caspase1

Caspase-1 is an enzyme in humans encoded by the CASP1 gene. It is a cysteine protease belonging to the inflammatory branch of the caspase family and plays a central role in the innate immune response. Caspase-1 is expressed in a variety of myeloid cells, including monocytes and macrophages, and is involved in processing inflammatory cytokines and mediating programmed cell death in response to cellular stress or infection.

The enzyme is produced as an inactive zymogen called procaspase-1, which contains a caspase recruitment domain (CARD) and a catalytic domain. Activation occurs within multiprotein complexes known as inflammasomes (for example, the NLRP3, NLRC4, and AIM2 inflammasomes). Upon inflammasome assembly and recruitment of the adaptor protein ASC, procaspase-1 undergoes autoproteolytic cleavage to generate an active enzyme composed of p20 and p10 subunits, typically functioning as a caspase-1 tetramer.

Activated caspase-1 cleaves the proforms of the inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) into their mature, secretable forms, thereby promoting inflammation. In addition, caspase-1 cleaves gasdermin D, producing an N-terminal fragment that forms membrane pores and drives pyroptotic cell death, a lytic form of programmed cell death that helps control infections but can contribute to inflammatory pathology if excessive.

Regulation of caspase-1 activity is a focus of therapeutic research. Inhibitors targeting caspase-1 have been explored for inflammatory and autoinflammatory diseases, and dysregulation of the caspase-1–inflammasome axis is implicated in various disorders, ranging from autoinflammatory syndromes to metabolic conditions.