These findings underline the critical role of Ubc9/PML/RNF4 axis in the pathomechanism of cardiac fibrosis and raise the possibility that SENP6 and SENP7, by counteracting RNF4 in PML SUMOylation (Figure 3), also contribute to this process providing potentially new therapeutic targets for the treatment of cardiac fibrosis and heart failure. The gene discussed is PML; the disease is heart failure.