CDH5 and cerebral cavernous malformation: The initial identification of KRIT1 as a Rap1 GTPase effector that interacts with the endothelial adherens junction (AJ) complex involving VE-cadherin, p120-catenin and β-catenin, and the discovery that loss of this protein promotes the weakening of VE-cadherin-mediated cell-cell adhesion and consequent dysfunction of the endothelial barrier, led to the original hypothesis that loss of blood-brain barrier (BBB) function contributes to the formation of CCM (Glading et al., 2007, Glading and Ginsberg, 2010).