PNPLA3-KO models did not generate a NASH phenotype, and thus, further knock-in experiments of PNPLA3-I148M reveal that an additional gain-of-function mechanism causes a lack of ubiquitination in PNPLA3-I148M resulting in a “gain-of-function” in reducing protein turnover [303,334]. Here, PNPLA3 is linked to metabolic dysfunction-associated steatohepatitis.