Finally, in response to feeding and insulin signaling, DNA-PKcs has been shown to transcriptionally upregulate genes involved in lipogenesis.28 In addition, DNA-PKcs mediates free-fatty-acid-induced lipid accumulation in hepatocytes, which may contribute to the pathogenesis of nonalcoholic steatohepatitis.29 In the present study, through a DNA-PKcs loss-of-function assay, we investigated the comprehensive role of DNA-PKcs in the etiology of ARLD with a particular focus on p53 activation, Drp1-required fission, and FUNDC1-related mitophagy. This evidence concerns the gene PRKDC and metabolic dysfunction-associated steatohepatitis.