The EFNB2-EPHB4-RASA1 signaling axis is important for human vascular diseases, such as CM-AVM and VOGM, as revealed by a series of research involving whole exome sequencing.39,40,91–93 In addition to malformed blood vessels, lymphatic abnormalities can be observed in some CM-AVM and VOGM patients, and EPHB4 mutations are found in lymphatic disorder CCLA patients.35,37 These findings indicate that EFNB2-EPHB4-RASA1 signaling regulates blood and lymphatic vessels in a complicated manner. Here, EFNB2 is linked to lymphatic system disorder.