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. The gene discussed is EPHB4; the disease is neoplasm.