To investigate the endothelial cell–specific role of oncogenic KRASG12D mutations in lymphangiectasia, we generated KrasG12Dfl/+; Cdh5CreERT2 mice, in which tamoxifen administration activates the gain-of-function KrasG12D allele specifically in Cdh5+ endothelial cells. The gene discussed is CDH5; the disease is lymphangiectasis.