This study, utilizing gsdmd−/− mice and gsdmd−/− microglia cells, highlights the precise function of GSDMD, main pyroptotic effector cell, and canonical or non-canonical inflammasome-dependent pyroptosis pathway in cerebral I/R injury, aiming to elucidate the mechanisms underlying GSDMD-mediated pyroptosis and to exploit new therapeutic targets for ischemic stroke. This evidence concerns the gene GSDMD and ischemic stroke.