Importantly, the crosstalk among Class I PI3K/Akt/mTOR and VPS34/mTOR pathway activation, associated with increased cell proliferation and pulmonary arterial remodeling in PAH, has previously been reported by us and others [7, 8, 14, 79, 85] and the mTOR inhibitor, sirolimus, is in clinical trials to treat pulmonary hypertension with positive results [86]. Here, PIK3C3 is linked to pulmonary arterial hypertension.