Gasdermins are key effectors of pyroptosis, a form of lytic programmed cell death initiated by inflammasomes. Inflammasomes detect cytosolic contamination or perturbation, activating caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane, causing cell swelling and rupture. Gasdermin D is one of six gasdermin family members; others, like gasdermin E, also form pores after cleavage. Pyroptosis eliminates compromised cells, removing pathogens and triggering inflammation. Engineered bacteria that evade inflammasomes reveal that pyroptosis kills the host cell but not the bacteria, trapping them in pore-induced intracellular traps (PITs). Neutrophils engulf and kill these trapped bacteria. Gasdermin D pores are large enough to release mature IL-1β and IL-18, explaining their release before cell lysis. The pore can also target bacterial membranes, killing bacteria in vitro. Gasdermins A, B, C, E, and DFNB59 are involved in various cellular processes, with mutations linked to diseases like deafness. Gasdermin E is activated by caspase-3, converting apoptosis into secondary necrosis. Pyroptosis is a critical defense mechanism against intracellular pathogens, but inappropriate activation can lead to diseases like deafness and sepsis. Understanding gasdermins and their roles in pyroptosis is essential for elucidating immune responses and developing therapeutic strategies.Gasdermins are key effectors of pyroptosis, a form of lytic programmed cell death initiated by inflammasomes. Inflammasomes detect cytosolic contamination or perturbation, activating caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane, causing cell swelling and rupture. Gasdermin D is one of six gasdermin family members; others, like gasdermin E, also form pores after cleavage. Pyroptosis eliminates compromised cells, removing pathogens and triggering inflammation. Engineered bacteria that evade inflammasomes reveal that pyroptosis kills the host cell but not the bacteria, trapping them in pore-induced intracellular traps (PITs). Neutrophils engulf and kill these trapped bacteria. Gasdermin D pores are large enough to release mature IL-1β and IL-18, explaining their release before cell lysis. The pore can also target bacterial membranes, killing bacteria in vitro. Gasdermins A, B, C, E, and DFNB59 are involved in various cellular processes, with mutations linked to diseases like deafness. Gasdermin E is activated by caspase-3, converting apoptosis into secondary necrosis. Pyroptosis is a critical defense mechanism against intracellular pathogens, but inappropriate activation can lead to diseases like deafness and sepsis. Understanding gasdermins and their roles in pyroptosis is essential for elucidating immune responses and developing therapeutic strategies.