In this study, we generated the first genetically engineered mouse model with a mARC1 A168T amino acid substitution, the murine ortholog of the human mARC1 A165T variant, and evaluated the impact of this substitution in multiple mouse models of MASH and liver fibrosis; additionally, we sought to characterize the sexual dimorphism of this mARC1 amino acid substitution in MASLD pathology. This evidence concerns the gene MTARC1 and metabolic dysfunction-associated steatohepatitis.