diff --git a/Marlin/SanityCheck.h b/Marlin/SanityCheck.h
index acbfe9560..a4c366507 100644
--- a/Marlin/SanityCheck.h
+++ b/Marlin/SanityCheck.h
@@ -1480,6 +1480,24 @@ static_assert(1 >= 0
   #error "HAVE_TMC2208 requires at least one TMC2208 stepper to be set."
 #endif
 
+/**
+ * TMC2208 software UART and ENDSTOP_INTERRUPTS both use pin change interrupts (PCI)
+ */
+#if ENABLED(HAVE_TMC2208) && ENABLED(ENDSTOP_INTERRUPTS_FEATURE) && !( \
+       ENABLED( X_HARDWARE_SERIAL  ) \
+    || ENABLED( X2_HARDWARE_SERIAL ) \
+    || ENABLED( Y_HARDWARE_SERIAL  ) \
+    || ENABLED( Y2_HARDWARE_SERIAL ) \
+    || ENABLED( Z_HARDWARE_SERIAL  ) \
+    || ENABLED( Z2_HARDWARE_SERIAL ) \
+    || ENABLED( E0_HARDWARE_SERIAL ) \
+    || ENABLED( E1_HARDWARE_SERIAL ) \
+    || ENABLED( E2_HARDWARE_SERIAL ) \
+    || ENABLED( E3_HARDWARE_SERIAL ) \
+    || ENABLED( E4_HARDWARE_SERIAL ) )
+  #error "select hardware UART for TMC2208 to use both TMC2208 and ENDSTOP_INTERRUPTS_FEATURE."
+#endif
+
 #if ENABLED(HYBRID_THRESHOLD) && DISABLED(STEALTHCHOP)
   #error "Enable STEALTHCHOP to use HYBRID_THRESHOLD."
 #endif
diff --git a/Marlin/pins_RAMPS.h b/Marlin/pins_RAMPS.h
index 9b10751e5..ff23a1964 100644
--- a/Marlin/pins_RAMPS.h
+++ b/Marlin/pins_RAMPS.h
@@ -131,7 +131,7 @@
   //#define E1_HARDWARE_SERIAL Serial1
   //#define E2_HARDWARE_SERIAL Serial1
   //#define E3_HARDWARE_SERIAL Serial1
-  //#define E3_HARDWARE_SERIAL Serial1
+  //#define E4_HARDWARE_SERIAL Serial1
 
   /**
    * Software serial