INSR and pulmonary emphysema: Endocytic dysfunction and altered intracellular trafficking and signaling of cell surface receptors such as TβRs, BMPR2 and tyrosine kinase receptors [i.e. vascular endothelial growth factor receptor (VEGF-R), platelet-derived growth factor receptor, (PDGF-R), insulin receptor (IR) etc.] have been implicated in the pathogenesis of PAH, emphysema and chronic obstructive pulmonary disease [24–27], pointing to implications of disrupted intracellular membrane trafficking in the pathobiology of vascular remodeling.