With its approval in 2011, the anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody ipilimumab started a new era of cancer treatment, as immune checkpoint inhibitors (ICIs) that primarily block programmed death 1 (PD-1) as well as CTLA-4 became the cornerstone of immunotherapy [1]. The gene discussed is CTLA4; the disease is cancer.