NLRC4 (NLR family CARD domain containing 4) is a key innate immune sensor that assembles inflammasome complexes to detect intracellular bacterial pathogens 1. As a nucleating protein, NLRC4 responds to specific bacterial proteins by oligomerizing with adaptor proteins to form the NLRC4 inflammasome, which activates caspase-1 and promotes production of pro-inflammatory cytokines IL-1β and IL-18, ultimately triggering pyroptotic cell death 2. Post-translational modifications regulate NLRC4 activation; SIRT3-mediated deacetylation at lysine residues 71 and 272 enhances inflammasome assembly and ASC speck formation, particularly during Salmonella typhimurium infection 3. Notably, NLRC4 can integrate with other inflammasome sensors (NLRP3, AIM2, Pyrin) to form multiprotein complexes that drive PANoptosis and amplify inflammatory responses to multiple pathogen-associated patterns 4. Unlike NLRP3, NLRC4 activation is not suppressed by β-hydroxybutyrate 5. Pathogenic NLRC4 variants cause autoinflammatory diseases including familial cold autoinflammatory syndrome 4 and autoinflammation with infantile enterocolitis 6, making it a potential therapeutic target for inflammasome-mediated disorders.