OX40L, also known as CD252, TNFSF4, or gp34, is a type II membrane protein that serves as the ligand for OX40 (CD134), a member of the tumor necrosis factor receptor (TNFR) superfamily. OX40L primarily expressed on antigen-presenting cells (APCs) such as dendritic cells, B cells, and macrophages, binds to OX40 on activated T cells, enhancing their activation, proliferation, and survival. The OX40-OX40L interaction can promote the production of various cytokines and enhance the effector functions of T cells, contributing to immune responses against pathogens and tumor. OX40 signaling can influence the differentiation and function of various T cell subsets, including Th1, Th2, Th17, Tfh, and regulatory T cells (Tregs). Its role in enhancing T cell responses makes it a target for cancer immunotherapy. Agonistic antibodies targeting OX40 are being developed to stimulate T cell responses against tumors. In conditions like rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease, the OX40-OX40L interaction contributes to the pathogenesis by promoting inflammatory T cell responses. The OX40-OX40L pathway also plays a role in transplant rejection and graft-versus-host disease (GVHD), making it a potential target for therapeutic intervention in transplantation medicine.