Figure 1.

The activation, pore formation, and repair mechanism of GSDMD. The activation of GSDMD is mainly divided into canonical, noncanonical, and other dependent pathways. The canonical pathway depends on caspase-1 via canonical inflammasomes; the noncanonical pathway depends on caspase-4/5/11 via lipopolysaccharide (LPS), while other pathways mainly depend on caspase-8. When stimulated by an external signal, these proteases cleave and activate GSDMD. GSDMDNT can then translocate to the plasma membrane and mitochondria and assemble into transmembrane pores. At the same time, activated forms of IL-1β and IL-18 are released through GSDMD pores to induce pyroptosis. Ca²⁺ influx can trigger the formation of the ESCRT complex and also promote caspase-7 and ASM to meet in the extracellular space, thereby initiating the membrane repair process.