Taken together, these findings lead to our hypothesis that extracellular HMGB1 acts as a pivotal mediator for PASMCs proliferation/migration and pulmonary vascular remodelling, these effects could be mediated by increased Drp1 phosphorylation and Drp1‐dependent mitochondrial fission through ERK1/2 signalling pathway, and subsequently promotes autophagy activation and BMPR2 lysosomal degradation and Id1 downregulation, thereby contributes to PAH development. Here, BMPR2 is linked to pulmonary arterial hypertension.