The main findings of this study include the following: (i) Chronic alcohol consumption is positively associated with hepatic NMNAT1 suppression, concomitant with a corresponding decrease in nuclear NAD+ content; (ii) IRF1 is a potential nuclear transcription factor of NMNAT1 and contributes to the alcohol-induced NMNAT1 decrease; (iii) Nmnat1-LKO aggravates hepatic steatosis and liver injury in ALD via a CSAD-associated pathway; (iv) Nmnat1-LOE alleviates ALD. The gene discussed is NMNAT1; the disease is fatty liver disease.