diff --git a/src/core/continuation.c b/src/core/continuation.c
index f9d933a553..64c4ae493b 100644
--- a/src/core/continuation.c
+++ b/src/core/continuation.c
@@ -35,6 +35,8 @@ void MVM_continuation_reset(MVMThreadContext *tc, MVMObject *tag,
         MVM_frame_special_return(tc, tc->cur_frame, clear_tag, NULL, tag_record, NULL);
         STABLE(code)->invoke(tc, code, null_args_callsite, tc->cur_frame->args);
     }
+
+    MVM_CHECK_CALLER_CHAIN(tc, tc->cur_frame);
 }
 
 void MVM_continuation_control(MVMThreadContext *tc, MVMint64 protect,
@@ -134,6 +136,8 @@ void MVM_continuation_control(MVMThreadContext *tc, MVMint64 protect,
     MVM_args_setup_thunk(tc, tc->cur_frame->return_value, tc->cur_frame->return_type, inv_arg_callsite);
     tc->cur_frame->args[0].o = cont;
     STABLE(code)->invoke(tc, code, inv_arg_callsite, tc->cur_frame->args);
+
+    MVM_CHECK_CALLER_CHAIN(tc, tc->cur_frame);
 }
 
 void MVM_continuation_invoke(MVMThreadContext *tc, MVMContinuation *cont,
@@ -192,6 +196,8 @@ void MVM_continuation_invoke(MVMThreadContext *tc, MVMContinuation *cont,
         MVM_args_setup_thunk(tc, cont->body.res_reg, MVM_RETURN_OBJ, null_args_callsite);
         STABLE(code)->invoke(tc, code, null_args_callsite, tc->cur_frame->args);
     }
+
+    MVM_CHECK_CALLER_CHAIN(tc, tc->cur_frame);
 }
 
 void MVM_continuation_free_tags(MVMThreadContext *tc, MVMFrame *f) {
diff --git a/src/core/frame.c b/src/core/frame.c
index ddef60f866..71c78b19f7 100644
--- a/src/core/frame.c
+++ b/src/core/frame.c
@@ -715,20 +715,7 @@ MVMFrame * MVM_frame_move_to_heap(MVMThreadContext *tc, MVMFrame *frame) {
     });
     });
     });
-#if MVM_GC_DEBUG
-    {
-        MVMFrame *check = new_cur_frame;
-        while (check) {
-            MVM_ASSERT_NOT_FROMSPACE(tc, check);
-            if ((check->header.flags & MVM_CF_SECOND_GEN) &&
-                    check->caller &&
-                    !(check->caller->header.flags & MVM_CF_SECOND_GEN) &&
-                    !(check->header.flags & MVM_CF_IN_GEN2_ROOT_LIST))
-                MVM_panic(1, "Gen2 -> Nursery after promotion without inter-gen set entry");
-            check = check->caller;
-        }
-    }
-#endif
+    MVM_CHECK_CALLER_CHAIN(tc, new_cur_frame);
 
     /* All is promoted. Update thread's current frame and reset the thread
      * local callstack. */
diff --git a/src/gc/debug.h b/src/gc/debug.h
index 15f73aeaea..9c613ca946 100644
--- a/src/gc/debug.h
+++ b/src/gc/debug.h
@@ -18,6 +18,19 @@
         cur_thread = cur_thread->body.next; \
     } \
 } while (0)
+#define MVM_CHECK_CALLER_CHAIN(tc, f) do { \
+    MVMFrame *check = f; \
+    while (check) { \
+        MVM_ASSERT_NOT_FROMSPACE(tc, check); \
+        if ((check->header.flags & MVM_CF_SECOND_GEN) && \
+                check->caller && \
+                !(check->caller->header.flags & MVM_CF_SECOND_GEN) && \
+                !(check->header.flags & MVM_CF_IN_GEN2_ROOT_LIST)) \
+            MVM_panic(1, "Illegal Gen2 -> Nursery in caller chain (not in inter-gen set)"); \
+        check = check->caller; \
+    } \
+} while (0)
 #else
 #define MVM_ASSERT_NOT_FROMSPACE(tc, c)
+#define MVM_CHECK_CALLER_CHAIN(tc, f)
 #endif
diff --git a/src/spesh/deopt.c b/src/spesh/deopt.c
index aaf9adbd91..32f04b2104 100644
--- a/src/spesh/deopt.c
+++ b/src/spesh/deopt.c
@@ -83,6 +83,7 @@ static void uninline(MVMThreadContext *tc, MVMFrame *f, MVMSpeshCandidate *cand,
                     uf->return_value = uf->work + last_res_reg;
 
                 /* Set up last uninlined's caller to us. */
+                MVM_ASSERT_NOT_FROMSPACE(tc, uf);
                 MVM_ASSIGN_REF(tc, &(last_uninlined->header), last_uninlined->caller, uf);
             }
             else {
@@ -91,6 +92,7 @@ static void uninline(MVMThreadContext *tc, MVMFrame *f, MVMSpeshCandidate *cand,
                 if (callee) {
                     /* Tweak the callee's caller to the uninlined frame, not
                      * the frame holding the inlinings. */
+                    MVM_ASSERT_NOT_FROMSPACE(tc, uf);
                     MVM_ASSIGN_REF(tc, &(callee->header), callee->caller, uf);
 
                     /* Copy over the return location. */
@@ -141,6 +143,7 @@ static void uninline(MVMThreadContext *tc, MVMFrame *f, MVMSpeshCandidate *cand,
             f->return_value = f->work + last_res_reg;
 
         /* Set up inliner as the caller, given we now have a direct inline. */
+        MVM_ASSERT_NOT_FROMSPACE(tc, f);
         MVM_ASSIGN_REF(tc, &(last_uninlined->header), last_uninlined->caller, f);
     }
     else {
@@ -224,6 +227,8 @@ void MVM_spesh_deopt_one(MVMThreadContext *tc, MVMuint32 deopt_target) {
             MVM_string_utf8_encode_C_string(tc, tc->cur_frame->static_info->body.name),
             MVM_string_utf8_encode_C_string(tc, tc->cur_frame->static_info->body.cuuid));
     }
+
+    MVM_CHECK_CALLER_CHAIN(tc, tc->cur_frame);
 }
 
 /* De-optimizes the current frame by directly specifying the addresses */
@@ -240,6 +245,8 @@ void MVM_spesh_deopt_one_direct(MVMThreadContext *tc, MVMuint32 deopt_offset,
         MVM_profiler_log_deopt_one(tc);
     clear_dynlex_cache(tc, f);
     deopt_frame(tc, tc->cur_frame, deopt_offset, deopt_target);
+
+    MVM_CHECK_CALLER_CHAIN(tc, tc->cur_frame);
 }
 
 /* De-optimizes all specialized frames on the call stack. Used when a change
@@ -340,4 +347,6 @@ void MVM_spesh_deopt_all(MVMThreadContext *tc) {
         l = f;
         f = f->caller;
     }
+
+    MVM_CHECK_CALLER_CHAIN(tc, tc->cur_frame);
 }