NOTCH2 (Neurogenic locus notch homolog protein 2) is a type 1 transmembrane protein involved in vascular, hepatic, renal, and neural development. Mutations in NOTCH2 are associated with Hajdu-Cheney syndrome, described by severe bone loss, and Alagille syndrome, characterized by a range of congenital dysfunctions of the liver and heart as well as bone malformations. In the normal developing brain, the NOTCH pathway is important for self-renewal and neural development, and expression of NOTCH proteins keeps neural progenitor cells in a proliferative state. In glioblastoma, NOTCH2 has been found to be upregulated and is thought to contribute to tumor cell proliferation. In immunohistochemistry, NOTCH2 has nuclear positivity in all tissues throughout the body. References: Genet. Test. 11 (3): 216–27, PMID: 17949281; Nature Genetics. 43 (4): 303–5, PMID: 21378985; Mol Med Rep. 2015 Jan;11(1):734-8, PMID: 25338527; Endocrine Reviews. 28 (3): 339–63, PMID: 17409286; Current Biology. 13 (15): 1348–54. doi:10.1016/S0960-9822(03)00492-5. PMID 12906797;