Identification of the endothelial signalling pathway of CCM3‐DLL4‐Notch‐EphB4‐Erk1/2 constitutes the mechanism of CCM3‐deficiency‐mediated angiogenesis and thus may potentially contribute to new therapeutic concepts in disrupting aberrant angiogenesis in human diseases such as CCM and hyper‐vascularized tumours. This evidence concerns the gene DLL4 and cerebral cavernous malformation.