Moreover, transcriptional profiling indicates that depletion of CXXC5 in Hep3B HCC cells is able to attenuate the expression of a significant portion of TGF‐β target genes, suggesting that CXXC5 is a novel positive feedback regulator of TGF‐β signaling.10 Moreover, the CXXC5 protein associates with the histone deacetylase HDAC1 in HCC cells and competes for Smad2/3 binding, therefore alleviating HDAC1‐mediated signaling inhibition. The gene discussed is SMAD2; the disease is hepatocellular carcinoma.