Mechanistically, the SMURF1/UVRAG-dependent autophagic flux is perturbed by counterbalancing modifications on UVRAG including direct deubiquitylation by zinc finger RANBP2-type containing 1 (ZRANB1) and phosphorylation by Casein Kinase 1 alpha 1 (CSNK1A1), thereby providing novel candidates for combined therapeutic intervention against HCC. Here, ZRANB1 is linked to hepatocellular carcinoma.