In addition to the three major conventional pathways already used in PAH therapy, targeting PDGF/PDGFR signaling, regulators in glycolytic metabolism, PI3K/AKT pathways, mitochondrial HSP90, HMGB1, and BET proteins by using their specific inhibitors, or a pharmacological induction of the p53 expression, could be attractive strategies for treating PAH (Figure 3). The gene discussed is HMGB1; the disease is pulmonary arterial hypertension.