The results show that while CRISPR–Cas9-mediated disruption of Cypor conferred APAP resistance and enabled the robust engraftment of gene-edited hepatocytes, achieving up to 13% liver engraftment, and reduced lipid levels, Cypor deficiency results in the accumulation of lipids in the liver and exacerbated steatosis in Ldlr−/− mice on a Western diet. The gene discussed is POR; the disease is steatosis.