Notch 2 functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBP-J kappa and activates genes of the enhancer of split locus. Notch 2 is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. It is expressed in the brain, heart, kidney, lung, skeletal muscle and liver. Defects in Nothch 2 are the cause of Alagille syndrome type 2 which is a multisystem disorder defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal and opthalmologic manifestations.