Development of hiPSC-based models derived from iPSC cells from healthy individuals or from patients harboring single nucleotide polymorphisms (SNP) that contribute to a high risk for developing NAFLD/NASH, such as the I148M mutation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene, offers the opportunity to study the cellular and molecular bases of NAFLD and to create robust cell platforms for drug discovery and translation to in vivo efficacy and toxicity [9]. Here, PNPLA3 is linked to metabolic dysfunction-associated steatohepatitis.