XIAP

XIAP is a core inhibitor of apoptosis protein that directly restrains executioner caspase-3 and caspase-7 through BIR2-region mechanisms and inhibits initiator caspase-9 through BIR3 binding^[1][2][3]. Mechanistically, its RING domain also supports E3 ubiquitin-ligase activity, linking XIAP biology to protein stability, apoptosis regulation, and non-apoptotic signaling contexts^[4]. In innate immune signaling, XIAP ubiquitylates RIPK2 and recruits LUBAC after NOD2 stimulation, thereby enabling NF-κB activation and proinflammatory cytokine secretion^[5]. In disease models and patient studies, XIAP deficiency associates with Crohn disease-like inflammatory bowel disease and defective NOD2 function in monocytes^[6]. Compared with related cIAP1 and cIAP2 isoforms, XIAP has the clearest biochemical role as a direct caspase inhibitor, whereas cIAP1 and cIAP2 bind but do not efficiently inhibit caspases^[7]. For experimental applications, selective XIAP antagonism can block NOD2-mediated inflammatory signaling by disrupting the XIAP-RIPK2 interaction, while broader IAP antagonists are used to test apoptosis sensitization mechanisms involving XIAP and cIAP proteins^[8][9].- XIAP directly controls caspase-dependent apoptosis and connects apoptosis biology with inflammatory NOD2 signaling^[1][5].- XIAP differs from cIAP1/cIAP2 because it directly inhibits caspase activity^[7].- XIAP-RIPK2 antagonism provides a practical model for studying NOD2-driven inflammation^[8].