Numb-like endocytic adaptor protein (NUMBL)

Numb-like endocytic adaptor protein (NUMBL, also called Numb-like protein) is a cytoplasmic adaptor/scaffolding protein highly homologous to Numb, involved in clathrin-mediated endocytosis, especially in neural and developmental contexts[2]. NUMBL contains a phosphotyrosine-binding (PTB) domain and several motifs enabling interactions with clathrin-adaptor AP-2 and endocytic accessory proteins, such as Eps15, regulating the sorting and internalization of various membrane receptors[2]. Unlike canonical membrane receptors or enzymes, NUMBL is not a druggable therapeutic target but is critical in modulating cell fate by antagonizing Notch receptor signaling through multiple mechanisms including receptor endocytosis and ubiquitin-mediated degradation[2][3]. Proper function of the Numb/NUMBL family ensures correct cell differentiation, migration, and tissue development. Loss of NUMBL/Numb function has been implicated in cancer—particularly through dysregulation of Notch and p53 signaling—and in neurodevelopmental abnormalities. While both Numb and NUMBL share roles in neural patterning, NUMBL lacks the proline-rich region present in Numb[2]. There are no known direct drugs targeting NUMBL, and it is not established as a direct biomarker or therapeutic target, though it is of interest in cancer and neurodevelopmental disorder biology.

Other names

Numb-like proteinNUMBLNumb-RNUMB-RCTG3aCAG3ATNRC23NUMBRNUMBLIKENumb-related proteinNBLnumb homolog-like