By contrast, lymphatic HIF-2α plays a crucial role in embryonic lymphatic development, adult lymphatic maintenance, and lymphatic regeneration in lymphedema by activating TIE2 signaling, which is required for lymphatic vascular maturation and maintenance (Dellinger et al., 2008; Kajiya et al., 2012; Kim et al., 2017; Jiang et al., 2020). The gene discussed is EPAS1; the disease is lymphedema.