Additionally, we review the involvement of non-Smad pathways in modulating hepatocyte responses to TGF-β-SF cytokines, particularly in the context of chronic liver diseases, as well as the interdependence with other key pathways (cholesterol metabolism, insulin resistance, oxidative stress and lipotoxicity) in MASLD/MASH pathogenesis. This evidence concerns the gene INS and metabolic dysfunction-associated steatotic liver disease.