To serve as a guide for future studies on medications that target ubiquitination and deubiquitination for the treatment of NAFLD, we present a review of the most recent research on E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs) and their mechanism of action in NAFLD. This evidence concerns the gene PRKN and metabolic dysfunction-associated steatotic liver disease.