The present review outlines the tripartite axis of mitophagy, namely, the PTEN-induced putative kinase 1/Parkin, PI3K/AKT/mTOR and AMP-activated protein kinase pathways, in NAFLD pathogenesis across the various stages of disease development, including steatosis, nonalcoholic steatohepatitis and fibrosis, and explores their therapeutic potential. This evidence concerns the gene PRKN and metabolic dysfunction-associated steatotic liver disease.