procaspase1

Procaspase-1 is the inactive zymogen form of caspase-1, an inflammatory cysteine protease that plays a central role in the innate immune response. It is synthesized as a single polypeptide containing an N-terminal caspase activation and recruitment domain (CARD) followed by a protease domain. After synthesis, procaspase-1 can dimerize and recruit to inflammasomes through CARD–CARD interactions, positioning it for activation.

Activation occurs when inflammasomes assemble in response to pathogenic or danger signals, bringing together sensor proteins such as NLRP3, AIM2, or NLRC4 and the adaptor ASC. Procaspase-1 undergoes autoproteolytic cleavage at specific aspartate residues, generating large (p20) and small (p10) catalytic subunits that assemble into an active caspase-1 tetramer. Active caspase-1 proteolytically processes pro-inflammatory cytokines pro-IL-1β and pro-IL-18 into their mature forms and cleaves gasdermin D (GSDMD), triggering pyroptotic cell death and cytokine release.

Procaspase-1 activity is tightly regulated; dysregulation can contribute to autoinflammatory diseases such as CAPS, gout, and atherosclerosis. Pharmacological inhibitors of caspase-1 and genetic studies continue to define its role in inflammation and host defense. This protease is a central node linking inflammasome signaling to downstream inflammatory responses.