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CONCLUSIONS These data uncover a novel physiological function of Hgs and support an essential role for the ESCRT machinery in the maintenance of EC polarity and cerebrovascular stability. TRANSLATIONAL PERSPECTIVE The structural and functional integrity of cerebral vasculature is critical for supporting normal brain function. Mutations of genes that play important roles in blood vessel development cause not only cardiovascular diseases, but also neurological disorders. In this study, we discovered a novel physiological function of Hgs in the maintenance of