TNFSF15 (TNF-like cytokine 1A/TL1A) is a TNF superfamily member that functions as a potent immunoregulatory cytokine with central roles in intestinal and systemic inflammation. The protein acts as a ligand for death receptor 3 (DR3) and decoy receptor 3 (DcR3), competitively binding to these receptors to mediate NF-κB activation and promote apoptosis 1. TNFSF15 is expressed by diverse immune cells (monocytes, macrophages, dendritic cells, T cells) and non-immune cells (synovial fibroblasts, endothelial cells), where it serves as a potent costimulator of effector immune responses and regulates T-cell proliferation, activation, cytokine, and chemokine production 12. Dysregulation of TNFSF15 is implicated in multiple autoimmune and inflammatory diseases, particularly inflammatory bowel disease (IBD), as well as rheumatoid arthritis, psoriasis, systemic lupus erythematosus, and ankylosing spondylitis 1. Genetic studies identify TNFSF15 as an IBD susceptibility locus with ancestry-dependent effects, showing differential effect sizes across European and East Asian populations 34. Clinically, anti-TL1A monoclonal antibodies (tulisokibart, TEV-48574) demonstrate therapeutic efficacy in Phase 2 trials for ulcerative colitis and Crohn's disease, reducing inflammation and fibrosis while preserving baseline immunity 567.