This study reveals that vascular endothelial protein tyrosine phosphatase (VE-PTP), a key regulator of endothelial barrier integrity, is a transcriptional target of HIF2A, and that HIF2A deletion in endothelial cells of mice exacerbates LPS-induced ALI, presumably due to the lack of VE-PTP regulation. The gene discussed is EPAS1; the disease is acute respiratory distress syndrome.