Immunotherapies targeting programmed death-1 (PD-1)/programmed death- ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), otherwise known as immune checkpoint inhibitors (ICIs), have revolutionized the therapeutic landscape of genitourinary malignancies such as renal cell carcinoma and urothelial carcinoma. The gene discussed is CTLA4; the disease is urothelial carcinoma.