Human and Cynomolgus Monkey CD40 Ligand (CD40L), also known as CD154 and encoded by the CD40LG gene, is a type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily, which includes related ligands such as TNF-α, CD27 ligand (CD70), OX40 ligand (CD252), and 4-1BB ligand (CD137L) that regulate immune activation and cell–cell signaling. In both humans (Homo sapiens) and cynomolgus monkeys (Macaca fascicularis), the CD40L protein is identical at the amino acid level, indicating strong evolutionary conservation and similar biological functions between these primate species. CD40L is primarily expressed on activated CD4⁺ T lymphocytes, and can also be detected on platelets and other activated immune cells following antigen stimulation. CD40L binds to its receptor CD40, which is expressed on B cells, dendritic cells, macrophages, and other antigen-presenting cells, initiating intracellular signaling pathways such as NF-κB and MAPK that promote B-cell activation, immunoglobulin class switching, germinal center formation, and development of long-lived memory B cells. Through these mechanisms, CD40L plays a central role in T cell–dependent antibody responses and regulation of adaptive immunity. Because cynomolgus monkeys share strong genetic and immunological similarity with humans, they are widely used as preclinical animal models for vaccine development, infectious diseases, and immunotherapy, and the identical CD40L sequence between these species supports their use in translational research on costimulatory signaling, immune regulation, and therapeutic targeting of the CD40–CD40L pathway.