In the last years the incremental comprehension of HCV tissue tropism and technological advances such as the popularization of gene knockouts have shed new light on the role of the lipoprotein synthesis pathway in HCV production, with three major findings: (i) Strikingly, ectopic ApoE expression efficiently complements the HCV production machinery in non-hepatoma cell lines (e.g., in the HEK 293T or HeLa cell backgrounds) that are otherwise incapable of producing infectious particles [121,122]. The gene discussed is APOE; the disease is hepatocellular carcinoma.