Moreover, based on reported venous-specific effects of inducible Tie2 deletion in retina (Chu et al., 2016) and over-activating TIE2 mutations in venous malformations (Kangas et al., 2018), Tie2 signaling appears particularly important to venous development that may contribute to the vessel-type-specific phenotype in Angpt4-/- mice. Here, ANGPT4 is linked to Venous malformation.