Sorafenib, a multi-tyrosine kinase inhibitor used in HCC treatment, and erastin, a ferroptosis inducer, enhance copper ionophore ES and ES-Cu-induced cuproptosis in HCC cells by promoting copper-dependent lipoylated protein aggregation, inhibiting FDX1 protein degradation, and decreasing intracellular GSH synthesis. The gene discussed is FDX1; the disease is hepatocellular carcinoma.