Pyroptosis was long regarded as caspase-1-mediated monocyte death in response to 
certain bacterial insults. Caspase-1 is activated upon various infectious and 
immunological challenges through different inflammasomes. The discovery of 
caspase-11/4/5 function in sensing intracellular lipopolysaccharide expands the 
spectrum of pyroptosis mediators and also reveals that pyroptosis is not cell 
type specific. Recent studies identified the pyroptosis executioner, gasdermin D 
(GSDMD), a substrate of both caspase-1 and caspase-11/4/5. GSDMD represents a 
large gasdermin family bearing a novel membrane pore-forming activity. Thus, 
pyroptosis is redefined as gasdermin-mediated programmed necrosis. Gasdermins 
are associated with various genetic diseases, but their cellular function and 
mechanism of activation (except for GSDMD) are unknown. The gasdermin family 
suggests a new area of research on pyroptosis function in immunity, disease, and 
beyond.