HES5 and pulmonary arterial hypertension: This review summarizes recent advancements in PAH therapy, emphasizing the integration of conventional medicine of the key pathways with nanoparticle-mediated drug delivery systems (nano-DDS), transforming growth factor beta/bone morphogenetic protein receptor type II, tyrosine kinase-based interventions, immunotherapies targeting inflammation and immune imbalance, and emerging molecular targets, including NOTCH3/HES-5 and E-selectin.