Caspase-12 (CASP12)

Caspase-12 is a cysteine protease located in the endoplasmic reticulum and closely related to the inflammatory caspase family, including caspase-1. In humans, its functional form is rare and primarily found in people of African descent; most others possess a truncated inactive version. Functionally, caspase-12 can negatively regulate caspase-1 and cytokine maturation, which impairs inflammatory responses, especially under septic conditions. It also plays roles in apoptosis, particularly related to ER stress. Due to its dominant-negative effects and population-specific functionality, caspase-12 is implicated in susceptibility to severe infections and sepsis. Mechanistically, its proteolytic activity is highly confined, mainly limited to auto-processing of its own proenzyme, distinguishing it from other caspases. Modulating its function may offer potential therapeutic avenues for diseases characterized by dysregulated inflammation or apoptosis[1][2][4][5].

Other names

Inactive caspase-12CASP12UNQ9415/PRO34398CASP-12Csp12L (full-length, active form)Csp12S (inactive, truncated form)

Inhibition or modulation of caspase-12 activity could attenuate its dominant-negative effect on caspase-1, thereby restoring inflammatory cytokine production and improving immune responses to sepsis[1][5]. Activating or mimicking caspase-12 function could theoretically reduce inflammatory damage by limiting cytokine storms[1].