Mutations in ANGPT2 and PIEZO1 and variants in the gene encoding the TIE1 receptor have been associated with lymphedema in patients, and loss-of-function mutations in Angpt2, Tie1, Tie2, Piezo1, Foxc2, and Gja4 lead to lymphatic defects in mice including failure of lymphatic valve formation, a process dictated by local OSS (3, 5–9, 18, 24, 25, 48–50). Here, TIE1 is linked to lymphedema.