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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 (CTLA-4 haploinsufficiency with autoimmune infiltration).