CASP5 is a cysteine protease that mediates pyroptosis, a lytic form of programmed cell death, by cleaving gasdermin-D (GSDMD) to release its N-terminal fragment, which forms membrane pores and triggers pyroptosis. The protein also processes and matures interleukin-18 during inflammasome activation. CASP5 functions as a pattern recognition receptor for lipopolysaccharide, directly binding LPS through its CARD domain and undergoing oligomerization upon LPS binding to initiate activation 1. It is a component of the inflammasome complex, where it works alongside caspase-1 and the adaptor protein ASC to mediate proinflammatory caspase activation and interleukin-1β processing 2. CASP5 expression is specifically regulated by lipopolysaccharide and interferon-gamma in immune cells 3. In disease contexts, CASP5 promotes pyroptosis in endothelial cells through the NF-κB-caspase-4/5-GSDMD pathway, contributing to atherosclerosis progression 4. In clear cell renal cell carcinoma, elevated CASP5 expression correlates with increased cell proliferation, migration, and tumor progression; conversely, CASP5 knockdown suppressed tumor growth and enhanced apoptosis 5. Clinically, CASP5 is targeted by emricasan, a caspase inhibitor, which may modulate pyroptosis-driven inflammation in relevant disease states.