Canine CTLA-4 (Cytotoxic T-Lymphocyte–Associated Protein 4, also known as CD152) is an immune checkpoint receptor belonging to the immunoglobulin superfamily that plays a key role in the negative regulation of T-cell activation in dogs (Canis lupus familiaris). CTLA-4 is primarily expressed on activated CD4⁺ and CD8⁺ T lymphocytes and on regulatory T cells (Tregs) following antigen stimulation. It functions by binding to the costimulatory ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells such as dendritic cells, macrophages, and B cells, competing with the activating receptor CD28 for these ligands. Engagement of CTLA-4 transmits inhibitory signals that suppress T-cell proliferation, cytokine production, and immune activation, helping maintain immune homeostasis and peripheral tolerance. In canine health, dysregulation of CTLA-4 signaling has been implicated in immune-mediated diseases and cancer, where tumor cells may exploit immune checkpoint pathways to evade immune detection. Dogs also serve as important comparative animal models for human cancer immunotherapy, particularly in canine melanoma, which closely resembles human melanoma in tumor biology and immune responses. Studies of CTLA-4–mediated immune regulation in dogs therefore contribute to veterinary oncology and translational immunotherapy research, helping to evaluate immune checkpoint–targeting therapies and mechanisms of T-cell regulation relevant to both canine and human cancer.