Swine CTLA-4 (Cytotoxic T-Lymphocyte–Associated Protein 4, also known as CD152) is an immune checkpoint receptor belonging to the immunoglobulin superfamily that functions as a key negative regulator of T-cell activation in pigs (Sus scrofa). CTLA-4 is primarily expressed on activated CD4⁺ and CD8⁺ T lymphocytes and on regulatory T cells (Tregs) following antigen stimulation. It binds 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, thereby helping maintain immune homeostasis and peripheral tolerance. In swine, CTLA-4 signaling is particularly relevant during viral infections such as porcine reproductive and respiratory syndrome virus (PRRSV), where excessive or dysregulated T-cell responses can influence disease outcome. Pigs are also used as large-animal models for transplantation immunology, and CTLA-4–Ig fusion proteins (similar to the human therapeutic abatacept/belatacept) have been tested in pig-to-nonhuman primate xenotransplantation studies, where blockade of CD28-mediated costimulation through the CTLA-4 pathway helps reduce T-cell–mediated graft rejection. These studies make swine CTLA-4 an important component of translational research on immune checkpoint regulation and tolerance induction in transplantation and immunotherapy.