Abstract
Regulated intramembrane proteolysis (RIP) is a highly conserved signaling paradigm whereby membrane-bound signaling proteins are cleaved in their transmembrane region and then released into the cytoplasm to act as signaling molecules. In most if not all cases intramembrane cleavage is preceded and regulated by a membrane proximal cleavage step called 'ectodomain shedding'. Here we will review the role of ectodomain shedding in RIP of the NOTCH signaling pathway, a highly conserved cell-cell communication pathway that mediates cell fate decisions during development and in adult tissues.