The prevailing hypothesis is the “multiple-hit” theory, which posits that MASLD arises from a confluence of genetic predispositions-such as variations in the transmembrane 6 superfamily member 2 gene and the patatin-like phospholipase domain-containing protein 3 gene-as well as epigenetic and other contributing factors, including IR, lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress (43, 44). The gene discussed is TM6SF2; the disease is metabolic dysfunction-associated steatotic liver disease.