A mechanistic study revealed that the overexpression of RTN3 inhibited the adenosine 5 monophosphate‐activated protein kinase (AMPK)–isocitrate dehydrogenase 2 (IDH2) pathway by altering the interaction between RTN3 and glucose‐regulated protein 78 (GRP78), inducing mitochondrial dysfunction, which ultimately promotes the genesis and development of NAFLD. The gene discussed is IDH2; the disease is metabolic dysfunction-associated steatotic liver disease.