Together these results reveal a mechanism of control of EC proliferation required for HHT pathogenesis, in which ALK1 signaling LOF increased endothelial cell cycle speed and progression via the overexpression of key mediators of the R point (including CDK6 and CDK2) to promote RB1 inactivation and S phase initiation (Fig. 2). Here, CDK2 is linked to hereditary hemorrhagic telangiectasia.