BRCC3 is a K63-specific deubiquitinase that plays critical roles in inflammation regulation and cellular signaling. As the catalytic subunit of the BRISC complex, BRCC3 specifically cleaves K63-linked polyubiquitin chains from target proteins 1. BRCC3 functions as a key regulator of NLRP3 inflammasome activation through deubiquitination of NLRP3, promoting inflammasome assembly and subsequent inflammatory responses 2345. In cardiovascular disease, BRCC3-mediated NLRP3 deubiquitination accelerates atherosclerosis in TET2-deficient macrophages, while BRCC3 also regulates vascular homeostasis by deubiquitinating ALK2 to maintain BMP signaling balance 26. The enzyme activates NF-κB signaling by promoting IκBα degradation and p65 nuclear translocation, contributing to inflammatory responses in conditions like pulpitis 7. BRCC3 demonstrates tissue-specific effects: it promotes inflammation in cerebral ischemia/reperfusion injury and inflammatory bowel disease through NLRP6 and NLRP3 activation respectively 45, while also regulating metabolic syndrome-induced arterial stiffness through PPM1B deubiquitination and TGF-β pathway activation 8. Bacterial pathogens can exploit BRCC3 function by targeting its complex components to manipulate host inflammatory responses 1.