C D40L (CD154) is a type II transmembrane protein and a member of the tumor necrosis factor (TNF) family. It exists as a trimer in membranes, held together through interactions within the extracellular domains of the protein. During an immune response, the TNF homology domains of the protein on T cells bind CD40 on antigen-presenting cells, an activity required for isotype switching from immunoglobulin M to immunoglobulin G. Accordingly, a defective CD40L gene is responsible for the X-linked hyper-IgM syndrome, a rare immunodeficiency disease characterized by the absence of circulating IgE or IgA, and germinal centers. Since its initial description on lymphocytes, a large body of evidence has been accumulating, demonstrating that CD40L is present on other vascular cells, where it plays a pivotal role in inflammation and thrombosis in various clinical conditions, such as atherothrombosis, immuno- inflammatory disease or cancer. . . .