TNFRSF14 is a TNF receptor superfamily member that functions as a co-stimulatory and co-inhibitory receptor in T cell regulation 1. It acts as a receptor for Herpes simplex virus 2, and its ligand TNFSF14/LIGHT engages TNFRSF14 to modulate immune responses across multiple contexts. In lymphoid malignancies, TNFRSF14 mutations are frequent in follicular lymphoma (39% of t(14;18)- cases) and are components of genetic subtypes in diffuse large B-cell lymphoma 23. TNFRSF14 signaling plays critical roles in immune homeostasis: the TNFSF14-TNFRSF14 axis regulates regulatory T cell (Treg) residence and function, with blocking TNFRSF14 reducing Tregs and enhancing anti-tumor CD8+ T cell responses in hepatocellular carcinoma models 4. During pregnancy, TNFRSF14 on decidual stromal cells is activated by dNK cell-derived TNFSF14, inhibiting pathological senescence and maintaining pregnancy viability 56. In cardiac pathology, TNFSF14-TNFRSF14 signaling promotes M2 macrophage polarization via the PI3Kγ/SGK1 pathway, driving cardiac fibrosis and atrial fibrillation 7. In imatinib-resistant gastrointestinal stromal tumors, the BTLA-TNFRSF14 axis between dendritic cells and myeloid cells contributes to immunosuppression 8. Thus, TNFRSF14 functions as a context-dependent regulator of T cell immunity and stromal-immune interactions with implications for cancer immunotherapy and reproductive biology.