TNFRSF25 (DR3) is a death domain-containing receptor that functions as a TNF receptor superfamily member with dual roles in immune regulation and apoptosis. The receptor binds its monogamous ligand TL1A (TNFSF15) and can be antagonized by the decoy receptor TR6/DcR3 1. TNFRSF25 mediates signaling through recruitment of TNFR-associated factor 2 and TNFR-associated death domain, leading to activation of NF-κB and PI3K/Akt pathways 2. The receptor serves as a broad-acting T cell costimulator, promoting IL-2 responsiveness and proinflammatory cytokine secretion in activated T cells 1. TNFRSF25 signaling provides constitutive proliferation signals to regulatory T cells through tonic self-antigen exposure while requiring foreign antigen for conventional T cell activation 2. In inflammatory bowel disease, TL1A-DR3 signaling plays a central role in intestinal inflammation, serving as a universal costimulator of effector immune responses while also regulating Tregs and innate lymphoid cells 34. The system demonstrates dichotomous roles, providing protective functions during acute mucosal injury but contributing to chr1 inflammatory responses and intestinal fibrosis 4. These diverse functions make TNFRSF25 a promising therapeutic target for autoimmune diseases and cancer immunotherapy 5.