The impact of these genetic variations alone or combined with MASLD pathogenesis has been investigated in hepatoma cells (HepG2) homozygous for the I148M PNPLA3 variant which were knocked-out (KO) for MBOAT7 (MBOAT7−/−), TM6SF2 (TM6SF2−/−), or both genes (MBOAT7−/−TM6SF2−/−) through the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology in order to mimic the human proteins’ loss-of-function phenotype. Here, PNPLA3 is linked to hepatocellular carcinoma.