Since MASLD occurs as a mitochondrial disease and the PNPLA3, MBOAT7 and TM6SF2 loss-of-function mutations seem to achieve a role in organelles’ dysfunction, in this study, we firstly investigated the impact of gene deletion on mitochondrial dynamism and integrity in KO HepG2 cells. The gene discussed is TM6SF2; the disease is metabolic dysfunction-associated steatotic liver disease.