Equine CD40 Ligand (CD40L), also known as CD154 and encoded by the CD40LG gene, is a type II transmembrane protein that belongs 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 intercellular signaling. In horses (Equus caballus), 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, proliferation, immunoglobulin class switching, germinal center formation, and development of memory B cells. Through these mechanisms, equine CD40L plays a central role in T cell–dependent antibody responses and regulation of adaptive immunity. In equine health, the CD40–CD40L signaling pathway contributes to immune responses against viral, bacterial, and parasitic pathogens, including those involved in equine influenza, equine herpesvirus infections, and other infectious diseases. Because CD40L-mediated costimulation is essential for effective humoral immunity and vaccine responses, equine CD40L is studied in veterinary immunology, infectious disease research, and vaccine development, helping to improve understanding of adaptive immune regulation and protective immunity in horses.