Emerging roles of palmitoylation in pyroptosis.

Pyroptosis is a lytic, proinflammatory type of programmed cell death crucial for the immune response to pathogen infections and internal danger signals. Gasdermin D (GSDMD) acts as the pore-forming protein in pyroptosis following inflammasome activation. While recent research has improved our understanding of pyroptosis activation and execution, many aspects regarding the molecular mechanisms controlling inflammasome and GSDMD activation remain to be elucidated. A growing body of literature has shown that S-palmitoylation, a reversible post-translational modification (PTM) that attaches palmitate to cysteine residues, contributes to multi-layered regulation of pyroptosis. This review summarizes the emerging roles of S-palmitoylation in pyroptosis research with a focus on mechanisms that regulate NLRP3 inflammasome and GSDMD activation.