We recently reported that the CXXC-type zinc finger domain-containing protein CXXC5 is transcriptionally upregulated by TGF-β/Smad signaling in HCC cells, and the CXXC5 protein in turn promotes TGF-β signaling by removing the histone deacetylase HDAC1 from activated Smad2/3, forming a novel positive feedback loop that plays a pivotal role in potentiating TGF-β-mediated growth inhibition of HCC cells [169]. The gene discussed is SMAD2; the disease is hepatocellular carcinoma.