Given that the characteristics of the gut microbiota population would serve as the most useful diagnostic biomarkers for NAFLD, as well as the low expression of ASPP2 has been demonstrated in NAFLD patients, our results not only provide evidence for a mechanism of ASPP2 on dysregulation of fatty acid metabolism and gut microbiota dysbiosis, but also demonstrate that ASPP2 is an important potential target for the treatment of NAFLD. Here, TP53BP2 is linked to metabolic dysfunction-associated steatotic liver disease.