The mitochondrial anchor syntaphilin (SNPH) is a key mitochondrial protein normally expressed in axons to maintain neuronal health by positioning mitochondria along axons for metabolic needs. However, in 2019 we discovered a novel form of excitotoxicity that results when SNPH is misplaced into neuronal dendrites in disease models. A key unanswered question about this SNPH excitotoxicity is the pathologic molecules that trigger misplacement or intrusion of SNPH into dendrites. Here, we identified two different classes of pathologic molecules that interact to trigger dendritic SNPH intrusion. Using primary hippocampal neuronal cultures from mice of either sex, we demonstrated that the pro-inflammatory cytokine IL-1β interacts with NMDA to trigger SNPH intrusion into dendrites. First, IL-1β and NMDA each individually triggers dendritic SNPH intrusion. Second, IL-1β and NMDA do not act independently but interact. Thus, blocking NMDAR by the antagonist MK-801 blocks IL-1β from triggering dendritic SNPH intrusio...