Inflammatory caspases (caspases 1, 4, 5, and 11) activate gasdermin D (GSDMD) to trigger pyroptosis, a form of inflammatory cell death. Cleavage of GSDMD produces an N-terminal fragment (GSDMD-NT) that forms membrane pores, leading to cell death and cytokine release. GSDMD-NT binds to specific lipids, including phosphatidylinositol phosphates, phosphatidylserine, and cardiolipin, and forms oligomers that create pores in cell membranes. Mutation of conserved basic residues in GSDMD-NT prevents pore formation and pyroptosis. GSDMD-NT is released during pyroptosis and can kill bacteria, suggesting a direct bactericidal effect. GSDMD-NT also kills intracellular bacteria, which may limit infection spread. The study shows that GSDMD-NT forms pores in membranes, leading to cell death and bacterial killing. The findings highlight the role of GSDMD-NT in pyroptosis and bacterial clearance.Inflammatory caspases (caspases 1, 4, 5, and 11) activate gasdermin D (GSDMD) to trigger pyroptosis, a form of inflammatory cell death. Cleavage of GSDMD produces an N-terminal fragment (GSDMD-NT) that forms membrane pores, leading to cell death and cytokine release. GSDMD-NT binds to specific lipids, including phosphatidylinositol phosphates, phosphatidylserine, and cardiolipin, and forms oligomers that create pores in cell membranes. Mutation of conserved basic residues in GSDMD-NT prevents pore formation and pyroptosis. GSDMD-NT is released during pyroptosis and can kill bacteria, suggesting a direct bactericidal effect. GSDMD-NT also kills intracellular bacteria, which may limit infection spread. The study shows that GSDMD-NT forms pores in membranes, leading to cell death and bacterial killing. The findings highlight the role of GSDMD-NT in pyroptosis and bacterial clearance.