Fig. 2. Gasdermins function as gatekeepers of pyroptosis.

In response to invasive pathogens, sterile danger signals or cytotoxic T cell attack, gasdermins (GSDMs) are activated by proteolytic cleavage, which releases the N-terminal (NT) fragment, which forms large cell membrane pores. The GSDM pore behaves as a gatekeeper for initiating downstream inflammatory cascades and pyroptotic cell death. Pyroptotic cells form large balloon-like membrane structures. Small intracellular molecules, including cytokines and cellular alarmins, are released through GSDM pores, causing inflammation. Some cells, termed ‘hyperactivated’, repair GSDM pores by shedding the damaged membrane and survive, but still induce inflammation by releasing IL-1 family cytokines.