[5][6] This gene encodes the third discovered human homologue of the Drosophila melanogaster type I membrane protein notch.

In Drosophila, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signalling pathway that plays a key role in neural development.

Mutations in NOTCH3 have been identified as the underlying cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

[7] Adult Notch3 knock-out mice show incomplete neuronal maturation in the spinal cord dorsal horn, resulting in permanently increased nociceptive sensitivity.

[10] Early clinical trials of Pfizer's PF-06650808, an anti-Notch3 antibody linked to a cytotoxic drug, showed efficacy against solid tumors.