Finally, from the translational perspective, to use circulating mitochondrial biomarkers for non-invasively predicting disease severity in genetically predisposed individuals, we compared the hepatic and peripheral bioenergetic profiles in MASLD patients carrying PNPLA3, MBOAT7 and/or TM6SF2 variations. The gene discussed is PNPLA3; the disease is metabolic dysfunction-associated steatotic liver disease.