Canine 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 cell–cell communication. In dogs (Canis lupus familiaris), 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, triggering intracellular signaling pathways such as NF-κB and MAPK that promote B-cell activation, immunoglobulin class switching, germinal center formation, and the development of memory B cells. Through these mechanisms, canine CD40L plays a key role in T cell–dependent antibody responses and regulation of adaptive immunity. In canine health, the CD40–CD40L pathway contributes to immune responses against viral, bacterial, and parasitic pathogens, and dysregulation of this signaling axis has been implicated in immune-mediated diseases and certain cancers. Because dogs develop several naturally occurring diseases that resemble human conditions, canine CD40L is also studied in comparative animal models of immune-mediated disease, cancer immunology, and vaccine responses, helping to advance understanding of costimulatory signaling and adaptive immune regulation in both veterinary and human medicine.