Caspase 12

Caspase-12 belongs to the inflammatory caspase group, but its biology differs from caspase-1, -4, -5, and -11 because it can attenuate endotoxin-induced cytokine production rather than directly promote cytokine maturation^[1][2]. Mechanistically, human full-length Caspase-12 reduced lipopolysaccharide-stimulated cytokine production in ex vivo whole blood and was linked to severe sepsis risk in African American individuals^[1]. In viral immunity, mouse Caspase-12 controlled West Nile virus infection by regulating TRIM25-mediated RIG-I ubiquitination and type I interferon production^[3]. ER-stress studies connect Caspase-12 with apoptosis, because overexpressed full-length caspase-12 underwent processing and ER-stress models showed caspase-12-associated caspase-3 activation^[4][5]. In intestinal inflammation, IKKα loss increased unfolded protein response and caspase-12 activation, reducing protective IL-18 secretion during acute colitis^[6]. Compared with caspase-1 and caspase-11, however, triple-knockout mouse data found no additional caspase-12 contribution to LPS response, apoptosis, necroptosis, or tunicamycin-induced ER stress in that model^[7]. For experimental applications, caspase-12 inhibition with Z-ATAD-FMK reduced oxygen-glucose-deprivation injury, apoptosis, NLRP3, caspase-1, IL-1β, and cleaved caspase-3 in primary astrocytes^[8].