diff --git a/include/pybind11/detail/internals.h b/include/pybind11/detail/internals.h
index 4ea374861e..cd3afdfe36 100644
--- a/include/pybind11/detail/internals.h
+++ b/include/pybind11/detail/internals.h
@@ -39,6 +39,7 @@
 /// further ABI-incompatible changes may be made before the ABI is officially
 /// changed to the new version.
 #ifndef PYBIND11_INTERNALS_VERSION
+//   REMINDER for next version bump: remove loader_life_support_tls
 #    define PYBIND11_INTERNALS_VERSION 11
 #endif
 
@@ -260,7 +261,7 @@ struct internals {
     PyObject *instance_base = nullptr;
     // Unused if PYBIND11_SIMPLE_GIL_MANAGEMENT is defined:
     thread_specific_storage<PyThreadState> tstate;
-    thread_specific_storage<loader_life_support> loader_life_support_tls;
+    thread_specific_storage<loader_life_support> loader_life_support_tls; // OBSOLETE (PR #5830)
     // Unused if PYBIND11_SIMPLE_GIL_MANAGEMENT is defined:
     PyInterpreterState *istate = nullptr;
 
diff --git a/include/pybind11/detail/type_caster_base.h b/include/pybind11/detail/type_caster_base.h
index 1b23c5c681..23d9407350 100644
--- a/include/pybind11/detail/type_caster_base.h
+++ b/include/pybind11/detail/type_caster_base.h
@@ -42,24 +42,40 @@ PYBIND11_NAMESPACE_BEGIN(detail)
 /// Adding a patient will keep it alive up until the enclosing function returns.
 class loader_life_support {
 private:
+    // Thread-local top-of-stack for loader_life_support frames (linked via parent).
+    // Observation: loader_life_support needs to be thread-local,
+    // but we don't need to go to extra effort to keep it
+    // per-interpreter (i.e., by putting it in internals) since
+    // individual function calls are already isolated to a single
+    // interpreter, even though they could potentially call into a
+    // different interpreter later in the same call chain.  This
+    // saves a significant cost per function call spent in
+    // loader_life_support destruction.
+    // Note for future C++17 simplification:
+    // inline static thread_local loader_life_support *tls_current_frame = nullptr;
+    static loader_life_support *&tls_current_frame() {
+        static thread_local loader_life_support *frame_ptr = nullptr;
+        return frame_ptr;
+    }
+
     loader_life_support *parent = nullptr;
     std::unordered_set<PyObject *> keep_alive;
 
 public:
     /// A new patient frame is created when a function is entered
     loader_life_support() {
-        auto &stack_top = get_internals().loader_life_support_tls;
-        parent = stack_top.get();
-        stack_top = this;
+        auto &frame = tls_current_frame();
+        parent = frame;
+        frame = this;
     }
 
     /// ... and destroyed after it returns
     ~loader_life_support() {
-        auto &stack_top = get_internals().loader_life_support_tls;
-        if (stack_top.get() != this) {
+        auto &frame = tls_current_frame();
+        if (frame != this) {
             pybind11_fail("loader_life_support: internal error");
         }
-        stack_top = parent;
+        frame = parent;
         for (auto *item : keep_alive) {
             Py_DECREF(item);
         }
@@ -68,7 +84,7 @@ class loader_life_support {
     /// This can only be used inside a pybind11-bound function, either by `argument_loader`
     /// at argument preparation time or by `py::cast()` at execution time.
     PYBIND11_NOINLINE static void add_patient(handle h) {
-        loader_life_support *frame = get_internals().loader_life_support_tls.get();
+        loader_life_support *frame = tls_current_frame();
         if (!frame) {
             // NOTE: It would be nice to include the stack frames here, as this indicates
             // use of pybind11::cast<> outside the normal call framework, finding such