In addition, the specific hormones with agonist/antagonist activity on the ER-α–PNPLA3-ERE1 axis in premenopausal versus postmenopausal women, in men and during liver disease progression need further investigations in in vivo models testing the impact of sex and estrogens on the phenotypic expression of the PNPLA3 p.I148M variant. The gene discussed is PNPLA3; the disease is liver disorder.