CASP5 (caspase-5) is a cysteine protease that mediates programmed cell death through multiple pathways. As a component of the inflammasome complex, CASP5 directly binds lipopolysaccharide (LPS) via its CARD domain and undergoes oligomerization to trigger pyroptosis, a lytic form of cell death 1. CASP5 executes pyroptosis by cleaving gasdermin-D (GSDMD), releasing its N-terminal fragment that forms membrane pores 2. The protein also processes pro-inflammatory cytokines IL-1β and IL-18 3, and participates in non-canonical inflammasome activation where it cleaves cGAS during antiviral responses. LPS and interferon-gamma specifically regulate CASP5 expression in immune cells 4. In disease pathogenesis, CASP5 upregulation promotes pyroptosis in endothelial cells via NF-κB signaling during atherosclerosis 2. Conversely, CASP5 shows paradoxical pro-tumorigenic effects in clear cell renal cell carcinoma, where high expression correlates with poor prognosis; CASP5 knockdown suppressed tumor cell growth and migration 5. CASP5 also modulates angiogenesis through VEGF-1 pathway activation 6. These dual roles suggest CASP5 functions context-dependently: protecting against infection and atherosclerosis through pyroptosis while supporting tumorigenesis in specific cancer types.