As previously discussed, inhibitors of cGMP degrading enzymes, in particular of PDE5A and PDE9A (some of which are currently approved for treatment of pulmonary arterial hypertension), enhance cGMP-driven effects and consequently increase cardiac muscle relaxation via PKG-mediated phosphorylation of TnI and titin ([1–5, 10, 19, 28, 31]; Fig. 1). The gene discussed is PDE5A; the disease is pulmonary arterial hypertension.