Using paired human hepatoma cell lines expressing PNPLA3 or PNPLA3-I148M at endogenous levels, we identify the Golgi apparatus as a central node in PNPLA3-I148M-driven cellular change and characterize alterations in LD-Golgi dynamics that translate to primary human hepatocytes. The gene discussed is PNPLA3; the disease is hepatocellular carcinoma.