diff --git a/lib/galaxy/managers/users.py b/lib/galaxy/managers/users.py
index 5ad3a7952b0..450aeff7620 100644
--- a/lib/galaxy/managers/users.py
+++ b/lib/galaxy/managers/users.py
@@ -17,7 +17,6 @@ from markupsafe import escape
 from sqlalchemy import (
     and_,
     exc,
-    func,
     select,
     true,
 )
@@ -316,24 +315,20 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
 
         :raises exceptions.Conflict: if any are found
         """
-        # TODO: remove this check when unique=True is added to the email column
-        if self.by_email(email) is not None:
+        if self.by_email(email, case_sensitive=False) is not None:
             raise exceptions.Conflict("Email must be unique", email=email)
 
     def by_id(self, user_id: int) -> Optional[model.User]:
         return self.app.model.session.get(self.model_class, user_id)
 
     # ---- filters
-    def by_email(self, email: str, filters=None, **kwargs) -> Optional[model.User]:
+    def by_email(self, email: str, case_sensitive: bool = True, deleted: bool | None = None) -> model.User | None:
         """
         Find a user by their email.
         """
-        filters = combine_lists(self.model_class.email == email, filters)
-        try:
-            # TODO: use one_or_none
-            return super().one(filters=filters, **kwargs)
-        except exceptions.ObjectNotFound:
-            return None
+        return get_user_by_email(
+            self.session(), email, self.model_class, case_sensitive=case_sensitive, deleted=deleted
+        )
 
     def by_api_key(self, api_key: str, sa_session=None):
         """
@@ -425,10 +420,10 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
         user = None
         if VALID_EMAIL_RE.match(identity):
             # VALID_PUBLICNAME and VALID_EMAIL do not overlap, so 'identity' here is an email address
-            user = get_user_by_email(self.session(), identity, self.model_class)
+            user = self.by_email(identity)
             if not user:
                 # Try a case-insensitive match on the email
-                user = self._get_user_by_email_case_insensitive(self.session(), identity)
+                user = self.by_email(identity, case_sensitive=False)
         else:
             user = get_user_by_username(self.session(), identity, self.model_class)
         return user
@@ -622,9 +617,9 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
         return None
 
     def get_reset_token(self, trans, email):
-        reset_user = get_user_by_email(trans.sa_session, email, self.app.model.User)
+        reset_user = self.by_email(email)
         if not reset_user:
-            reset_user = self._get_user_by_email_case_insensitive(trans.sa_session, email)
+            reset_user = self.by_email(email, case_sensitive=False)
         if reset_user and not reset_user.deleted:
             prt = self.app.model.PasswordResetToken(reset_user)
             trans.sa_session.add(prt)
@@ -660,7 +655,10 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
             return None
         if getattr(self.app.config, "normalize_remote_user_email", False):
             remote_user_email = remote_user_email.lower()
-        user = get_user_by_email(self.session(), remote_user_email, self.app.model.User)
+        user = self.by_email(remote_user_email)
+        if not user:
+            # Try a case-insensitive match on the email
+            user = self.by_email(remote_user_email, case_sensitive=False)
         if user:
             # Ensure a private role and default permissions are set for remote users (remote user creation bug existed prior to 2009)
             self.app.security_agent.get_private_user_role(user, auto_create=True)
@@ -669,13 +667,14 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
                     self.app.security_agent.user_set_default_permissions(user)
                     self.app.security_agent.user_set_default_permissions(user, history=True, dataset=True)
         elif user is None:
+            session = self.session()
             random.seed()
-            user = self.app.model.User(email=remote_user_email)
+            username = username_from_email(session, remote_user_email, self.model_class)
+            user = self.model_class(email=remote_user_email, username=username)
             user.set_random_password(length=12)
             user.external = True
-            user.username = username_from_email(self.session(), remote_user_email, self.app.model.User)
-            self.session().add(user)
-            self.session().commit()
+            session.add(user)
+            session.commit()
             self.app.security_agent.create_private_user_role(user)
             # We set default user permissions, before we log in and set the default history permissions
             if self.app_type == "galaxy":
@@ -683,10 +682,6 @@ class UserManager(base.ModelManager, deletable.PurgableManagerMixin):
             # self.log_event( "Automatically created account '%s'", user.email )
         return user
 
-    def _get_user_by_email_case_insensitive(self, session, email):
-        stmt = select(self.app.model.User).where(func.lower(self.app.model.User.email) == email.lower()).limit(1)
-        return session.scalars(stmt).first()
-
 
 class UserSerializer(base.ModelSerializer, deletable.PurgableSerializerMixin):
     model_manager_class = UserManager
diff --git a/lib/galaxy/model/db/user.py b/lib/galaxy/model/db/user.py
index 00f824f5e1e..16ce1dff810 100644
--- a/lib/galaxy/model/db/user.py
+++ b/lib/galaxy/model/db/user.py
@@ -1,6 +1,11 @@
-from typing import Optional
+from collections.abc import (
+    Iterable,
+    Sequence,
+)
+from typing import TYPE_CHECKING
 
 from sqlalchemy import (
+    and_,
     false,
     func,
     or_,
@@ -12,10 +17,12 @@ from galaxy.model import (
     Role,
     User,
 )
-from galaxy.model.scoped_session import galaxy_scoped_session
+
+if TYPE_CHECKING:
+    from sqlalchemy.orm import scoped_session
 
 
-def get_users_by_ids(session: galaxy_scoped_session, user_ids):
+def get_users_by_ids(session: "scoped_session", user_ids: Iterable[int]) -> Sequence[User]:
     stmt = select(User).where(User.id.in_(user_ids))
     return session.scalars(stmt).all()
 
@@ -24,29 +31,33 @@ def get_users_by_ids(session: galaxy_scoped_session, user_ids):
 # the tool_shed app, which has its own User model, which is different from
 # galaxy.model.User. In that case, the tool_shed user model should be passed as
 # the model_class argument.
-def get_user_by_email(session, email: str, model_class=User, case_sensitive=True):
+def get_user_by_email(
+    session: "scoped_session", email: str, model_class=User, case_sensitive: bool = True, deleted: bool | None = None
+) -> User | None:
     filter_clause = model_class.email == email
     if not case_sensitive:
-        filter_clause = func.lower(model_class.email) == func.lower(email)
+        filter_clause = func.lower(model_class.email) == email.lower()
+    if deleted is not None:
+        filter_clause = and_(filter_clause, model_class.deleted == deleted)
     stmt = select(model_class).where(filter_clause).limit(1)
     return session.scalars(stmt).first()
 
 
-def get_user_by_username(session, username: str, model_class=User):
+def get_user_by_username(session: "scoped_session", username: str, model_class=User) -> User | None:
     stmt = select(model_class).filter(model_class.username == username).limit(1)
     return session.scalars(stmt).first()
 
 
 def get_users_for_index(
-    session,
+    session: "scoped_session",
     deleted: bool,
-    f_email: Optional[str] = None,
-    f_name: Optional[str] = None,
-    f_any: Optional[str] = None,
+    f_email: str | None = None,
+    f_name: str | None = None,
+    f_any: str | None = None,
     is_admin: bool = False,
     expose_user_email: bool = False,
     expose_user_name: bool = False,
-):
+) -> Sequence[User]:
     stmt = select(User)
     if f_email and (is_admin or expose_user_email):
         stmt = stmt.where(User.email.like(f"%{f_email}%"))
@@ -69,7 +80,7 @@ def get_users_for_index(
     return session.scalars(stmt).all()
 
 
-def _cleanup_nonprivate_user_roles(session, user, private_role_id):
+def _cleanup_nonprivate_user_roles(session: "scoped_session", user: User, private_role_id: int) -> None:
     """
     Delete UserRoleAssociations EXCEPT FOR THE PRIVATE ROLE;
     Delete sharing roles that are associated with this user only;
diff --git a/lib/galaxy/visualization/genomes.py b/lib/galaxy/visualization/genomes.py
index f7ae75be582..2c7195a0523 100644
--- a/lib/galaxy/visualization/genomes.py
+++ b/lib/galaxy/visualization/genomes.py
@@ -376,6 +376,7 @@ class Genomes:
         dbkey_owner, dbkey = decode_dbkey(dbkey)
         if dbkey_owner:
             dbkey_user = get_user_by_username(trans.sa_session, dbkey_owner)
+            assert dbkey_user is not None
         else:
             dbkey_user = trans.user
 
diff --git a/lib/galaxy/webapps/base/webapp.py b/lib/galaxy/webapps/base/webapp.py
index a894c83fa75..495affb05e8 100644
--- a/lib/galaxy/webapps/base/webapp.py
+++ b/lib/galaxy/webapps/base/webapp.py
@@ -626,7 +626,7 @@ class GalaxyWebTransaction(base.DefaultWebTransaction, context.ProvidesHistoryCo
                     galaxy_session_requires_flush = True
                 elif (
                     remote_user_email
-                    and galaxy_session.user.email != remote_user_email
+                    and galaxy_session.user.email.lower() != remote_user_email.lower()
                     and (
                         not self.app.config.allow_user_impersonation
                         or remote_user_email not in self.app.config.admin_users_list
diff --git a/lib/galaxy/webapps/galaxy/services/quotas.py b/lib/galaxy/webapps/galaxy/services/quotas.py
index 564f864d599..c45f7742c7c 100644
--- a/lib/galaxy/webapps/galaxy/services/quotas.py
+++ b/lib/galaxy/webapps/galaxy/services/quotas.py
@@ -131,7 +131,13 @@ class QuotasService(ServiceBase):
             try:
                 return trans.security.decode_id(item)
             except Exception:
-                return get_user_by_email(trans.sa_session, item).id
+                user = get_user_by_email(trans.sa_session, item)
+                if not user:
+                    # Try a case-insensitive match on the email
+                    user = get_user_by_email(trans.sa_session, item, case_sensitive=False)
+                if not user:
+                    raise ValueError(f"User with email address '{item}' not found.")
+                return user.id
 
         def get_group_id(item):
             try:
diff --git a/lib/galaxy/webapps/galaxy/services/sharable.py b/lib/galaxy/webapps/galaxy/services/sharable.py
index 57cce95213a..cdc92fa74cf 100644
--- a/lib/galaxy/webapps/galaxy/services/sharable.py
+++ b/lib/galaxy/webapps/galaxy/services/sharable.py
@@ -4,8 +4,6 @@ from typing import (
     Union,
 )
 
-from sqlalchemy import false
-
 from galaxy.managers import base
 from galaxy.managers.sharable import (
     SharableModelManager,
@@ -156,9 +154,12 @@ class ShareableService:
                 email_address = email_or_id.strip()
                 if not email_address:
                     continue
-                send_to_user = self.manager.user_manager.by_email(
-                    email_address, filters=[User.table.c.deleted == false()]
-                )
+                send_to_user = self.manager.user_manager.by_email(email_address, deleted=False)
+                if not send_to_user:
+                    # Try a case-insensitive match on the email
+                    send_to_user = self.manager.user_manager.by_email(
+                        email_address, case_sensitive=False, deleted=False
+                    )
 
             if not send_to_user:
                 send_to_err.add(f"{email_or_id} is not a valid Galaxy user.")
diff --git a/test/integration/test_user_preferences.py b/test/integration/test_user_preferences.py
index 62e76aa108a..4bc715a55ef 100644
--- a/test/integration/test_user_preferences.py
+++ b/test/integration/test_user_preferences.py
@@ -21,6 +21,7 @@ class TestUserPreferences(integration_util.IntegrationTestCase):
         app = cast(Any, self._test_driver.app if self._test_driver else None)
 
         db_user = get_user_by_email(app.model.session, user["email"])
+        assert db_user is not None
 
         # create some initial data
         put(url)
diff --git a/test/unit/app/managers/test_UserManager.py b/test/unit/app/managers/test_UserManager.py
index 04a5662e6e4..90844e233c5 100644
--- a/test/unit/app/managers/test_UserManager.py
+++ b/test/unit/app/managers/test_UserManager.py
@@ -31,7 +31,6 @@ user2_data = dict(email="user2@user2.user2", username="user2", password=default_
 user3_data = dict(email="user3@user3.user3", username="user3", password=default_password)
 user4_data = dict(email="user4@user4.user4", username="user4", password=default_password)
 uppercase_email_user = dict(email="USER5@USER5.USER5", username="USER5", password=default_password)
-lowercase_email_user = dict(email="user5@user5.user5", username="user5", password=default_password)
 
 
 # =============================================================================
@@ -74,12 +73,23 @@ class TestUserManager(BaseTestCase):
         self.log("emails must be unique")
         with self.assertRaises(exceptions.Conflict):
             self.user_manager.create(
-                **dict(email="user2@user2.user2", username="user2a", password=default_password),
+                email=user2_data["email"],
+                username="user2a",
+                password=default_password,
+            )
+        self.log("emails must be case-insensitive unique")
+        with self.assertRaises(exceptions.Conflict):
+            self.user_manager.create(
+                email=user2_data["email"].capitalize(),
+                username="user2a",
+                password=default_password,
             )
         self.log("usernames must be unique")
         with self.assertRaises(exceptions.Conflict):
             self.user_manager.create(
-                **dict(email="user2a@user2.user2", username="user2", password=default_password),
+                email="user2a@user2.user2",
+                username=user2_data["username"],
+                password=default_password,
             )
 
     def test_trimming(self):
@@ -250,27 +260,10 @@ class TestUserManager(BaseTestCase):
         assert uppercase_user.username == uppercase_email_user["username"]
         assert self.user_manager.get_user_by_identity(uppercase_user.email) == uppercase_user
         assert self.user_manager.get_user_by_identity(uppercase_user.username) == uppercase_user
-        # Create another user with the same email just differently capitalized.
-        # This is not normally allowed now, since registration goes through user_manager.register(),
-        # which checks for that, but was possible in earlier releases of Galaxy
-        lowercase_user = self.user_manager.create(**lowercase_email_user)
-        assert lowercase_user.email == lowercase_email_user["email"]
-        assert lowercase_user.username == lowercase_email_user["username"]
-        assert self.user_manager.get_user_by_identity(lowercase_user.email) == lowercase_user
-        assert self.user_manager.get_user_by_identity(lowercase_user.username) == lowercase_user
-        # assert uppercase user can still be retrieved
-        assert self.user_manager.get_user_by_identity(uppercase_user.email) == uppercase_user
-        assert self.user_manager.get_user_by_identity(uppercase_user.username) == uppercase_user
         # username matches need to be exact
-        assert self.user_manager.get_user_by_identity(uppercase_user.username.capitalize()) is None
-        # email matches can ignore capitalization
-        ignore_email_capitalization_user = self.user_manager.create(
-            email="user123@nopassword.com", username="someusername123"
-        )
-        assert (
-            self.user_manager.get_user_by_identity(ignore_email_capitalization_user.email.capitalize())
-            == ignore_email_capitalization_user
-        )
+        assert self.user_manager.get_user_by_identity(uppercase_email_user["username"].capitalize()) is None
+        # Email lookups should be case-insensitive
+        assert self.user_manager.get_user_by_identity(uppercase_email_user["email"].capitalize()) == uppercase_user
 
 
 # =============================================================================
diff --git a/test/unit/data/model/db/conftest.py b/test/unit/data/model/db/conftest.py
index 182b667daf4..357933a9f2a 100644
--- a/test/unit/data/model/db/conftest.py
+++ b/test/unit/data/model/db/conftest.py
@@ -37,7 +37,7 @@ def engine(db_url: str) -> "Engine":
 @pytest.fixture
 def session(engine: "Engine") -> Session:
     session = Session(engine)
-    # For sqlite, we need to explicitly enale foreign key constraints.
+    # For sqlite, we need to explicitly enable foreign key constraints.
     if engine.name == "sqlite":
         session.execute(text("PRAGMA foreign_keys = ON;"))
     return session