The activation of mitochondrial SIRT5 contributes to the promotion of growth and metastasis of HCC cells via glucose metabolism reprogramming from oxidative phosphorylation to glycolysis.439 The possible explanation for the dual role of SIRT5 in HCC could be related to its involvement in different metabolic processes, including glucose and lipid metabolism, which might result in opposite effects on tumor progression.3 In addition to mitochondrial SIRTs, the nonmitochondrial SIRTs can influence HCC by regulating cancer-related metabolism, especially glucose metabolism. Here, SIRT5 is linked to cancer.