DLL4 (Delta-like protein 4) is a type I membrane protein that belongs to the DSL (Delta/Serrate/Lag2) family of Notch ligands and plays an important role in vascular development.? There are five Notch ligands (DLL1, DLL3, DLL4, Jagged-1 and Jagged-2) and four Notch receptors (Notch-1 to Notch-4) in mammals.? Interactions of Notch receptors with their ligands result in sequential proteolysis by ADAM (disintegrin metalloprotease) and then by presenilin/ gamma secretase, resulting in the shedding of the extracellular domains and the generation of soluble ICD (intracellular domain) signaling fragments. The Notch ICD translocates to the nucleus and interacts with transcriptional factors to promote the transcription of target genes. The ICDs of the Notch ligands have also been shown to translocate to the nucleus upon binding its receptor. DLL4 is induced by VEGF (vascular growth factor) and functions as a downstream modulator of VEGF mediated angiogenesis. DLL4/Notch signaling restrains the excessive branching and sprouting of endothelials in response to VEGF signaling. Deletion of a single copy of DLL4 results in severe vascular defects and embryonic lethality, indicating the essential role of DLL4/Notch signaling in vascular development. DLL4 is also up-regulated in tumour vasculature and the blockade of DLL4/Notch signaling inhibits tumour growth by increasing functionally defective vasculature.