Pyroptosis is the process of inflammatory cell death.The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection.Excessive pyropto-sis,however,leads to several inflammatory diseases,including sepsis and autoimmune disorders.Pyrop-tosis can be canonical or noncanonical.Upon microbe infection,the canonical pathway responds to pathogen-associated molecular patterns(PAMPs)and damage-associated molecular patterns(DAMPs),while the noncanonical pathway responds to intracellular lipopolysaccharides(LPS)of Gram-negative bacteria.The last step of pyroptosis requires the cleavage of gasdermin D(GsdmD)at D275(numbering after human GSDMD)into N-and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11(caspase 4/5 in humans,caspase 11 in mice)in the noncanonical pathway.Upon cleavage,the N-terminus of GsdmD(GsdmD-N)forms a transmembrane pore that releases cytokines such as IL-1β and IL-18 and disturbs the regulation of ions and water,eventually resulting in strong inflammation and cell death.Since GsdmD is the effector of pyroptosis,promising inhibitors of GsdmD have been developed for inflamma-tory diseases.This review will focus on the roles of GsdmD during pyroptosis and in diseases.