Genetic studies in Drosophila have identified Numb as an inhibitor of Notch signaling during development of the peripheral and central nervous systems as well as muscle cell differentiation. Both Drosophila and mammalian Numb are asymmetrically localized in dividing precursor cells, ensuring that cells adopt distinct cell fates through suppression of Notch signaling in one daughter cell (Rhyu et al. 1994). NUMB recruits E3 ubiquitin ligase ITCH (AIP4) to NOTCH1 and promotes sorting of NOTCH1 through late endosomes for degradation (McGill et al. 2009).