The regulation of the expression of oncogenes and/or tumor suppressors by macroH2A1 in hepatocytes could be particularly relevant for the development of HCC associated with metabolic syndrome since the activity of these genes often mechanically connects NAFLD to the onset of HCC; therefore, macroH2A1 isoforms, in addition to being proposed as markers for lung, breast, and skin cancer, could play a key role in the pathogenesis of liver cancer as well [22,23,24]. Here, MACROH2A1 is linked to metabolic dysfunction-associated steatotic liver disease.