In pulmonary arterial hypertension (PAH), PDE5 inhibitors (sildenafil, tadalafil) are recommended as first-line therapy by both ESC/ERS and AHA/ACC guidelines (Class I, Level A), due to their efficacy in improving exercise capacity, symptoms, and hemodynamics [76,77]. The gene discussed is PDE5A; the disease is pulmonary arterial hypertension.