Norrin cystine knot growth factor (NDP)

Norrin cystine knot growth factor (NDP) is a secreted, cysteine-rich protein that forms a unique homodimer with each subunit adopting a cystine knot fold[1][2][3]. Norrin functions as an atypical Wnt ligand, activating Wnt/β-catenin signaling specifically through binding Frizzled-4 receptor and Lrp5/6 co-receptors, which is crucial for vascular development in the retina, cochlea, and central nervous system[1][2][3][4]. Mutations in the NDP gene cause Norrie disease and related disorders characterized by retinal vascularization defects, progressive vision loss, and sometimes hearing impairment or intellectual disability[4]. Norrin's role is essential in retinal angiogenesis and the maintenance of blood–retinal barrier integrity. There are no marketed drugs directly targeting Norrin, but its signaling pathway is of significant research interest for inherited vascular diseases of the eye.

Other names

NorrinNDPEVR2Norrie disease proteinX-linked exudative vitreoretinopathy 2 proteinFEVRND

Ligand for Frizzled-4 receptor: Binds to Frizzled-4 (Fz4) and co-receptors Lrp5/6, activating the canonical Wnt/β-catenin signaling pathway, promoting vascular development[1][2][3]