GDF-15’s effects on muscle in vitro appear to be mediated by proteolysis and the activation of TAK1 since inhibition of both the 26S ribosomal protein unit and the kinase, by a specific inhibitor, suppressed GDF-15-induced myotube atrophy, making TAK1 inhibition an attractive target to prevent muscle loss in PAH. The gene discussed is GDF15; the disease is pulmonary arterial hypertension.