TNFRSF4 (OX40) is a TNF receptor superfamily member functioning as a T cell co-stimulatory molecule that plays critical roles in immune regulation and inflammatory responses. As a primary function, TNFRSF4 acts as a receptor for OX40 ligand (OX40L/TNFSF4) expressed on antigen-presenting cells and activated T cells 1. Mechanistically, OX40-OX40L interactions promote T cell survival, effector differentiation, and memory formation while enhancing production of pro-inflammatory cytokines including IFNγ 12. TNFRSF4 is preferentially expressed on activated T cells and regulatory T cells (Tregs) 1, with specific Treg subsets displaying high TNFRSF4 expression coupled with enhanced suppressive capacity 3. In disease contexts, TNFRSF4+ Tregs with activated immunosuppressive function and clonal expansion associate with resistance to anti-PD-1 immunotherapy in esophageal and nasopharyngeal carcinomas 45. Conversely, TNFRSF4 expression is upregulated in atopic dermatitis, where OX40-OX40L signaling amplifies T cell-mediated inflammation, making it a validated therapeutic target 2. The TNFRSF4-TNFSF4 axis represents a key immune checkpoint interaction pair with therapeutic potential across multiple cancer and inflammatory disease contexts 6.