Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a receptor on T Helper cells that functions as an immune checkpoint and downregulator of immune responses. Mutations in CTLA-4 are associated with insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, Graves' disease, systemic lupus erythematosus (SLE), celiac disease, primary biliary cirrhosis, thyroid-associated orbitopathy, multiple sclerosis, and other autoimmune diseases. The spliced variant of CTLA-4 in SLE is present in the patient's serum. Haploinsufficiency of CTLA-4 causes the immune system disorder known as CTLA-4 deficiency or CHAI disease (CTLA4 haploinsufficiency with autoimmune infiltration).

CTLA-4 and CD28, together with their ligands B7-1 and B7-2, constitute one of the dominant costimulatory pathways that regulate T- and B-cell responses. CTLA-4 and CD28 are structurally homologous molecules that are members of the immunoglobulin (Ig) gene superfamily. Both CTLA-4 and CD28 are composed of a single Ig V‑like extracellular domain, a transmembrane domain and an intracellular domain.