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. The gene discussed is PRKN; the disease is metabolic dysfunction-associated steatohepatitis.