IRS1 and metabolic dysfunction-associated steatotic liver disease: In 2010, Dongiovanni et al. reported that two variants affecting the action of insulin receptor—Lys121Gln in Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1/PC-1) and the Gly972Arg in Insulin Receptor Substrate 1 (IRS-1) genes—were significantly associated with NAFLD and the presence of fibrosis in a population of obese adults [42].