GSDME, also known as DFNA5 (deafness, autosomal dominant 5), is a member of the gasdermin family of pore-forming proteins. In its full-length form, GSDME is autoinhibited. Upon apoptotic stimulation, active caspase-3 specifically cleaves GSDME at a conserved aspartate residue, Asp270 (D270). This cleavage of Gasdermin E separates the N‑terminal pore‑forming domain from the C‑terminal repressor domain. The released N‑terminal fragment then inserts into the plasma membrane, forms large pores, and induces a lytic, inflammatory form of cell death known as pyroptosis. Therefore, Asp270 cleavage is a critical molecular switch that converts caspase‑3‑mediated apoptosis into pyroptosis, linking GSDME/DFNA5 to cancer therapy, chemotherapy‑induced toxicity, and hearing loss pathology.