NOTCH4(NOTCH, DROSOPHILA, HOMOLOG OF, 4) also known as INT3 or NOTCH3, FORMERLY, is a member of the Notch family. In situ hybridization revealed that Notch4 transcripts are primarily restricted to endothelial cells in embryonic and adult life, suggesting a specific role forNotch4 during development of vertebrate endothelium. The sequences of the mouse and human NOTCH4 proteins are 82% identical. Northern blot analysis revealed that NOTCH4(S) is the major transcript and is expressed in a wide variety of tissues. Fluorescence in situ hybridization confirmed the location of the NOTCH4 gene at chromosome 6p21.3. In linkage disequilibrium mapping of the MHC region in 80 British parent-offspring trios, Wei and Hemmings (2000) found that NOTCH4 was highly associated with schizophrenia. Repression of Notch4 resolved ataxia and reversed the disease progression, demonstrating that Notch4 is not only sufficient to induce but also required to sustain the disease.