CD40LG encodes CD40 ligand, a critical immunoregulatory protein expressed on activated T cells and other immune cells. The primary function of CD40LG is to bind CD40 receptor on B cells, dendritic cells, and other antigen-presenting cells, facilitating essential immune interactions 1. This CD40-CD40LG interaction is required for T cell-dependent B cell activation, proliferation, and differentiation, as well as dendritic cell licensing to activate CD8+ T cells 2. The signaling pathway involves NF-κB activation and production of various cytokines and chemokines 1. CD40LG deficiency causes X-linked hyper-IgM syndrome type 1, characterized by decreased IgG, IgA, and IgE with normal or elevated IgM levels, leading to recurrent sinopulmonary infections and opportunistic pathogens 3. Novel mutations like c.156 G>T can cause disease through nonsense-mediated mRNA decay 4. In autoimmune diseases like systemic lupus erythematosus, CD40LG is overexpressed due to DNA hypomethylation, leading to excessive B cell stimulation and IgG production 5. The clinical significance extends to cancer therapy, where CD40 agonists are being investigated as immunotherapeutic agents 2, and CD40LG expression serves as a prognostic marker in lung adenocarcinoma 6.