Gomez-Puerto MC, van Zuijen I, Huang CJZ, et al. - Researchers examined the contribution of autophagy in the degradation of BMPR2 in pulmonary vascular cells. Degradation of endogenous BMPR2 through the lysosome in primary human pulmonary artery endothelial and smooth muscle cells was exhibited, ie, two cell types that play a principal role in the pathology of the disease. Through an elegant HaloTag system, a block in lysosomal degradation results in heightened levels of BMPR2 at the plasma membrane. Moreover, pharmacological or genetic manipulations of autophagy permitted the investigators to conclude that autophagy activation contributes to BMPR2 degradation. However, additional investigation whether the role of autophagy in the degradation of BMPR2 is direct or through the modulation of the endocytic pathway is needed. Interestingly, using an iPSC-derived endothelial cell model, it was suggested that BMPR2 heterozygosity alone is enough to cause an enhanced autophagic flux. Besides BMPR2 heterozygosity, in lung vascular cells, pro-inflammatory cytokines also add to augmented autophagy. Moreover, an elevation in microtubule-associated protein 1 light chain 3 beta levels in lung sections from Pulmonary arterial hypertension (PAH) induced in rats was explicated. Accordingly, from end-stage idiopathic PAH patients, pulmonary microvascular endothelial cells impersonate an increased autophagic flux. Therefore, a model in which an elevated autophagic flux in PAH patients adds to a higher reduction in BMPR2 levels was exhibited. Collectively, the basic mechanisms of BMPR2 degradation and a critical role for autophagy in PAH were highlighted in this study.