Because TM4SF5 is involved in the development of chronic liver diseases, including MASLD,40,41 MASH,25 fibrosis,23 portal hypertension,42 and HCC,21,29 chalcone-based small molecules36 and monoclonal antibodies22,43 targeting TM4SF5 have been under development for clinical benefits; systemic or hepatocyte-specific overexpression of TM4SF5 in mice promotes chronic liver diseases in diet- or chemical-mediated liver malignancy models, whereas systemic Tm4sf5−/− knockout mice show fewer MASLD features and less HCC development. Here, TM4SF5 is linked to metabolic dysfunction-associated steatohepatitis.