As demonstrated by Kettner et al., both deletionof core clock genes (including BMAL1, Per1/Per2, or Cry1/Cry2) and chronic jetlag could inducehepatomegaly, nonalcoholic fatty liver disease (NAFLD), and even spontaneoushepatocellular carcinoma (HCC) with a sufficient induction period.16 The authors revealed that chronic circadiandisruption could cause dysregulation of the sympathetic nervous system(SNS), which results in activation of the constitutive androstanereceptor (CAR) and inhibition of the Farnesoid X receptor (FXR). Here, PER2 is linked to metabolic dysfunction-associated steatotic liver disease.