TGF-β signaling in hepatocyte is implicated in liver fibrosis and carcinogenesis. While the C-terminal phosphorylation of SMAD3 by TGFBR1 may be tumor-suppressive, oncogenic linker-phosphorylated SMAD3 signaling is involved in both nonalcoholic steatohepatitis-related HCC and HBV/HCV-related HCC [22–24]. The gene discussed is SMAD3; the disease is hepatocellular carcinoma.