The treatment of metastatic melanoma has been revolutionized in the past decade because of the development of agents that target elements in the immune system including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed cell death protein ligand 1 (PD-L1).[1] Checkpoint inhibitors (CPI) have played a fundamental role in melanoma treatment; however, many patients remain refractory. The gene discussed is CTLA4; the disease is melanoma.