GSDMD (gasdermin D) is a pore-forming protein that serves as the key executioner of pyroptosis, a programmed inflammatory cell death pathway. GSDMD functions through cleavage by inflammatory caspases (caspase-1, -4, -5, and -11), which removes autoinhibition and releases the active N-terminal domain that forms membrane pores 1. These pores facilitate the release of inflammatory cytokines like IL-1β and induce pyroptotic cell death 1. Recent findings reveal that GSDMD activation also requires S-palmitoylation at Cys191, which is enhanced by reactive oxygen species and mediated by palmitoyltransferases ZDHHC5 and ZDHHC9 2. Beyond its classical pyroptotic function, GSDMD exhibits tissue-protective roles by mediating the secretion of pro-healing metabolites like 11,12-epoxyeicosatrienoic acid from macrophages, promoting tissue regeneration 3. In pathological contexts, GSDMD contributes to blood-brain barrier disruption during sepsis through endothelial cell pyroptosis 4 and drives inflammation-related tissue damage in various diseases 5. Therapeutically, GSDMD can be targeted by compounds like disulfiram, which inhibits pore formation 6, or activated by small molecules to enhance antitumor immunity 7.