Notch3 is one of the four mammalian Notch proteins that serve as signaling receptors and are involved in developmental patterning, cell fate decisions, and the regulation of cell survival and proliferation. Notch3 interacts with membrane-bound ligands Jagged1, Jagged2, and Delta1 to regulate cell fate determination. Upon ligand activation, the Notch intracellular domain (NICD) is released and forms a transcriptional activator complex with RBPJ/RBPSUH, which in turn activates genes within the enhancer of split locus. As a result, the activation of Notch3 can initiate differentiation, proliferation, and apoptotic programs.