Caspase-4
Caspase-4 is a human inflammatory caspase that, together with its paralog Caspase-5, corresponds functionally to murine Caspase-11 and operates in the noncanonical inflammasome pathway. Its CARD-containing proenzyme binds lipopolysaccharide directly, an unusual property among human proteins that allows cytosolic detection of Gram-negative bacterial infection. Upon activation, Caspase-4 cleaves gasdermin D, launching pyroptosis and the release of inflammatory mediators including IL-1β through secondary mechanisms. Genetic variation affecting CASP4 has been linked to susceptibility to severe sepsis, and the protease has become a focus of drug discovery aimed at curbing endotoxin-driven inflammation while preserving antibacterial defenses.
