Numb proteins (Numblike and Numb) display a complex pattern of functions such as the control of asymmetric cell division, cell fate choice, endocytosis, cell adhesion, and cell migration. They have been shown to inhibit Notch signaling by stimulating endocytosis of Notch.
Numb and Numblike have at least partially distinct functions. Numblike is a negative regulator of the NF-κB signaling pathway by abrogating TRAF5-induced activation of NF-κB. Recently, Numblike was implicated as a physiologically relevant target of microRNA miR-34a in neural progenitor cells allowing for enhanced Notch signaling and inhibition of neuronal differentiation.
Numb and Numblike are essential in maintaining neural progenitor cells during early neurogenesis by allowing cells to choose progenitor over neuronal fates. They were recently also discovered to be involved in cardiac morphogenesis.