diff --git a/changelog.d/10826.misc b/changelog.d/10826.misc
new file mode 100644
index 000000000000..53e56fc362f3
--- /dev/null
+++ b/changelog.d/10826.misc
@@ -0,0 +1,2 @@
+Opt out of cache expiry for `get_users_who_share_room_with_user`, to hopefully improve `/sync` performance when you
+haven't synced recently.
diff --git a/synapse/storage/databases/main/roommember.py b/synapse/storage/databases/main/roommember.py
index 9beeb96aa98d..a4ec6bc32897 100644
--- a/synapse/storage/databases/main/roommember.py
+++ b/synapse/storage/databases/main/roommember.py
@@ -162,7 +162,7 @@ def _check_safe_current_state_events_membership_updated_txn(self, txn):
                 self._check_safe_current_state_events_membership_updated_txn,
             )
 
-    @cached(max_entries=100000, iterable=True)
+    @cached(max_entries=100000, iterable=True, prune_unread_entries=False)
     async def get_users_in_room(self, room_id: str) -> List[str]:
         return await self.db_pool.runInteraction(
             "get_users_in_room", self.get_users_in_room_txn, room_id
@@ -439,7 +439,7 @@ async def get_local_current_membership_for_user_in_room(
 
         return results_dict.get("membership"), results_dict.get("event_id")
 
-    @cached(max_entries=500000, iterable=True)
+    @cached(max_entries=500000, iterable=True, prune_unread_entries=False)
     async def get_rooms_for_user_with_stream_ordering(
         self, user_id: str
     ) -> FrozenSet[GetRoomsForUserWithStreamOrdering]:
@@ -544,7 +544,12 @@ async def get_rooms_for_user(
         )
         return frozenset(r.room_id for r in rooms)
 
-    @cached(max_entries=500000, cache_context=True, iterable=True)
+    @cached(
+        max_entries=500000,
+        cache_context=True,
+        iterable=True,
+        prune_unread_entries=False,
+    )
     async def get_users_who_share_room_with_user(
         self, user_id: str, cache_context: _CacheContext
     ) -> Set[str]:
diff --git a/synapse/util/caches/deferred_cache.py b/synapse/util/caches/deferred_cache.py
index f05590da0d54..6262efe07235 100644
--- a/synapse/util/caches/deferred_cache.py
+++ b/synapse/util/caches/deferred_cache.py
@@ -73,6 +73,7 @@ def __init__(
         tree: bool = False,
         iterable: bool = False,
         apply_cache_factor_from_config: bool = True,
+        prune_unread_entries: bool = True,
     ):
         """
         Args:
@@ -105,6 +106,7 @@ def metrics_cb() -> None:
             size_callback=(lambda d: len(d) or 1) if iterable else None,
             metrics_collection_callback=metrics_cb,
             apply_cache_factor_from_config=apply_cache_factor_from_config,
+            prune_unread_entries=prune_unread_entries,
         )
 
         self.thread: Optional[threading.Thread] = None
diff --git a/synapse/util/caches/descriptors.py b/synapse/util/caches/descriptors.py
index 1ca31e41ac61..b9dcca17f1a6 100644
--- a/synapse/util/caches/descriptors.py
+++ b/synapse/util/caches/descriptors.py
@@ -258,6 +258,7 @@ def __init__(
         tree=False,
         cache_context=False,
         iterable=False,
+        prune_unread_entries: bool = True,
     ):
         super().__init__(orig, num_args=num_args, cache_context=cache_context)
 
@@ -269,6 +270,7 @@ def __init__(
         self.max_entries = max_entries
         self.tree = tree
         self.iterable = iterable
+        self.prune_unread_entries = prune_unread_entries
 
     def __get__(self, obj, owner):
         cache: DeferredCache[CacheKey, Any] = DeferredCache(
@@ -276,6 +278,7 @@ def __get__(self, obj, owner):
             max_entries=self.max_entries,
             tree=self.tree,
             iterable=self.iterable,
+            prune_unread_entries=self.prune_unread_entries,
         )
 
         get_cache_key = self.cache_key_builder
@@ -507,6 +510,7 @@ def cached(
     tree: bool = False,
     cache_context: bool = False,
     iterable: bool = False,
+    prune_unread_entries: bool = True,
 ) -> Callable[[F], _CachedFunction[F]]:
     func = lambda orig: DeferredCacheDescriptor(
         orig,
@@ -515,6 +519,7 @@ def cached(
         tree=tree,
         cache_context=cache_context,
         iterable=iterable,
+        prune_unread_entries=prune_unread_entries,
     )
 
     return cast(Callable[[F], _CachedFunction[F]], func)
diff --git a/synapse/util/caches/lrucache.py b/synapse/util/caches/lrucache.py
index 39dce9dd4166..17cb98ff0b9a 100644
--- a/synapse/util/caches/lrucache.py
+++ b/synapse/util/caches/lrucache.py
@@ -202,10 +202,11 @@ def __init__(
         cache: "weakref.ReferenceType[LruCache]",
         clock: Clock,
         callbacks: Collection[Callable[[], None]] = (),
+        prune_unread_entries: bool = True,
     ):
         self._list_node = ListNode.insert_after(self, root)
-        self._global_list_node = None
-        if USE_GLOBAL_LIST:
+        self._global_list_node: Optional[_TimedListNode] = None
+        if USE_GLOBAL_LIST and prune_unread_entries:
             self._global_list_node = _TimedListNode.insert_after(self, GLOBAL_ROOT)
             self._global_list_node.update_last_access(clock)
 
@@ -314,6 +315,7 @@ def __init__(
         metrics_collection_callback: Optional[Callable[[], None]] = None,
         apply_cache_factor_from_config: bool = True,
         clock: Optional[Clock] = None,
+        prune_unread_entries: bool = True,
     ):
         """
         Args:
@@ -427,7 +429,15 @@ def cache_len():
         self.len = synchronized(cache_len)
 
         def add_node(key, value, callbacks: Collection[Callable[[], None]] = ()):
-            node = _Node(list_root, key, value, weak_ref_to_self, real_clock, callbacks)
+            node = _Node(
+                list_root,
+                key,
+                value,
+                weak_ref_to_self,
+                real_clock,
+                callbacks,
+                prune_unread_entries,
+            )
             cache[key] = node
 
             if size_callback: