Patients with MASLD were significantly older and had higher BMI values compared to controls, both in wild-type subjects and in those carrying the PNPLA3 variant; however, plasma lipids and fasting blood LAL activity differed significantly between patients with MASLD and controls only in the presence of the PNPLA3 variant. Here, PNPLA3 is linked to metabolic dysfunction-associated steatotic liver disease.