TNFRSF6B encodes a decoy receptor that functions as a negative regulator of apoptosis and inflammation by neutralizing cytotoxic TNF family ligands. The protein binds and neutralizes TNFSF6 (FasL), TNFSF14 (LIGHT), and TNFSF15, thereby blocking their pro-apoptotic and inflammatory signaling 1. In functional studies, TL1A (TNFSF15) was identified as a DR3 and TR6/DcR3 (TNFRSF6B) ligand, with TR6-Fc protein antagonizing NF-κB activation and apoptosis induced by TL1A 1. TNFRSF6B demonstrates significant clinical relevance across multiple diseases. Genetic variants are associated with sporadic IgA nephropathy susceptibility 2. In hepatocellular carcinoma, TNFRSF6B expression negatively correlates with apoptosis, and anti-TNFRSF6B neutralizing antibodies decrease proliferation, arrest cell cycle, and induce apoptosis in cancer cells 3. Mendelian randomization studies identify TNFRSF6B as a potential therapeutic target, showing protective effects against prostate cancer 4 and associations with allergic diseases including atopic asthma and atopic dermatitis 5. Additionally, TNFRSF6B serves as a biomarker for cardiovascular health-related dementia risk 6 and imminent lung cancer diagnosis 7. These findings establish TNFRSF6B as a critical regulator with therapeutic potential across inflammatory, oncologic, and cardiovascular conditions.