XIAP is a multifunctional E3 ubiquitin ligase and direct caspase inhibitor that regulates cell survival, immunity, and cellular homeostasis. Structurally, XIAP directly binds the active site pockets of caspase-3 and caspase-7, obstructing substrate entry, while inactivating caspase-9 by maintaining its monomeric state 12. As an E3 ligase, XIAP ubiquitinates diverse substrates including RIPK1, RIPK2, and MAP3K proteins, modulating NF-κB and MAPK signaling pathways 34. XIAP critically regulates innate immunity by catalyzing Lys-63-linked polyubiquitination of RIPK2 downstream of NOD1/NOD2 pattern recognition receptors, orchestrating antibacterial responses and intestinal inflammation control 56. In cancer, XIAP upregulation promotes progression through multiple mechanisms. Recent evidence shows XIAP ubiquitinates the m6A reader YTHDC1, degrading it to enhance MMP-2 expression and bladder cancer metastasis 7. XIAP also ubiquitinates YTHDC1 and other substrates to regulate cell survival signaling, autophagy, and necroptosis 8. XIAP deficiency causes severe immunological consequences, including inflammatory bowel disease and hemophagocytic lymphohistiocytosis through dysregulated caspase-8-driven apoptosis and pyroptotic crosstalk 910. Defective autophagy and NLRP3 inflammasome hyperactivation drive IL-1β-mediated hyperinflammation in patient macrophages 10.