SIRT5 desuccinylates and inhibits acyl‐CoA oxidase 1 (ACOX1), a peroxisomal enzyme whose overactivity causes ROS‐mediated DNA damage as well as alteration of fatty acid β‐oxidation and redox homeostasis, ultimately leading to the onset of HCC.177. Here, ACOX1 is linked to hepatocellular carcinoma.