Gasdermin E (GSDME/DFNA5) cleavage at D270 by caspase‑3 (CASP3) or by granzyme B (GZMB ) liberates the N‑terminal fragment of GSDME (GSDME(1-270)), which moves to the plasma membrane where it strongly binds to inner leaflet lipids such as phosphatidylinositol (4,5)‑bisphosphate (Rogers C et al. 2017; Wang Y et al. 2017). Residues 1–56 of GSDME include 19 hydrophobic ones thought to be involved in membrane targeting and penetration (Rogers C et al. 2017). Upon cleavage by CASP3, the liberated N‑terminal fragment of GSDME forms pores in the plasma membrane to either drive cells directly into pyroptosis or induce secondary necrosis after apoptosis in cells with low expression level of GSDME (that is insufficient to override the CASP3-mediated apoptotic program) (Rogers C et al. 2017; Wang Y et al. 2017).