Notch4 is a member of the Notch family. The Notch4 signaling network is an evolutionarily conserved intracellular pathway that regulates physical cell to cell interactions. The Notch4 protein, once cleaved from the trans-Golgi network, is presented on the cell surface as a heterodimer. Notch4 regulates cell-fate determination as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1. In Drosophila, once these ligands are activated via the release of the notch intracellular domain (NICD), Notch4 forms a transcriptional activator complex with RBPJ/RBPSUH which then activates the genes of the Enhancer of Split (E(spl)) locus. Notch4 also plays a role in vascular, renal and hepatic development, the implementation of differentiation, proliferation and apoptotic programs, and the regulation of branching morphogenesis in the development of the vascular system.