TNFSF4

TNFSF4 encodes Tumor Necrosis Factor Superfamily Member 4, commonly known as OX40 ligand (OX40L) or CD252. This type II transmembrane protein is expressed on antigen-presenting cells (APCs) like dendritic cells and macrophages. It binds to its receptor OX40 (CD134) on activated T cells, delivering a critical co-stimulatory signal that drives T cell proliferation, survival, cytokine secretion (e.g., IL-2, IFN-γ), and memory T cell development.
Dysregulation of the OX40L-OX40 pathway contributes to autoimmune diseases (rheumatoid arthritis, multiple sclerosis) and cancer. Therapeutic strategies include anti-OX40L monoclonal antibodies (e.g., roxalimumab) for autoimmunity to dampen overactive T cells, and OX40 agonists for cancer immunotherapy to enhance anti-tumor T cell responses, with several candidates in clinical trials.