Neurogenic locus notch homolog 4 receptor (Notch4)

The **Neurogenic locus notch homolog 4 receptor (Notch4)** is a type I transmembrane protein and a member of the Notch family of cell surface receptors[1][5]. It is encoded by the *NOTCH4* gene on chromosome 6 and contains an extracellular domain composed of multiple epidermal growth factor-like (EGF) repeats and an intracellular domain with regulatory modules for signal transduction[1][2]. Notch4 is predominantly expressed in vascular endothelial cells, where it modulates angiogenesis, vascular remodeling, and endothelial cell survival[3][4][5]. It plays a key role in cell fate decisions via the evolutionarily conserved Notch signaling pathway, which regulates crosstalk between adjacent cells[1][2]. Notch4 is implicated in several pathological conditions including breast cancer (especially therapy-resistant and stem cell-enriched tumors), melanoma, head and neck cancers, and vascular disease[5]. It is being researched as a potential therapeutic target, largely by inhibiting its signaling using gamma-secretase inhibitors, though such strategies face safety and specificity challenges due to the pathway’s roles in normal physiology[2][5].

Other names

Notch 4NOTCH4Neurogenic locus notch homolog 4

Notch pathway inhibition (e.g., gamma-secretase inhibitors prevent Notch receptor activation, blocking downstream signaling); potential cis-inhibition of Notch1 signaling by Notch4 extracellular domain[3]