Immune checkpoint inhibitors (ICPIs) targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) pathway are the two most studied immunotherapy mechanisms in HCC (Figure 1). The gene discussed is CTLA4; the disease is hepatocellular carcinoma.