Upon caspase 3 activation, GSDME-deficient cells (e.g., GSDME knockout, HeLa cells and Jurkat T cells) first undergo apoptosis followed by secondary necrosis at later stages, whilst cells expressing high GSDME level (e.g., GSDME overexpression, neuroblastoma cells, and skin melanoma cells) proceed rapidly to membrane permeabilisation via similar mechanisms as MLKL and GSDMD (3). The gene discussed is GSDME; the disease is cutaneous melanoma.