NDP (norrin) is a secreted cystine knot growth factor that plays a central role in retinal vascularization and inner ear development by activating canonical Wnt signaling. NDP binds to the frizzled receptor FZD4 on vascular endothelial cells, with TSPAN12 serving as a co-receptor 1. This binding stabilizes β-catenin (CTNNB1), activating LEF/TCF-mediated transcription programs essential for endothelial cell function 2. In the cochlea, NDP signaling maintains the vascular blood-barrier, regulates endothelial biomarker expression (Cldn5, Abcb1a, Slc7a1, Slc7a5), and prevents sensory hair cell death 1. Pathogenic NDP variants cause Norrie disease, an X-linked recessive disorder characterized by congenital retinal vascular dysgenesis leading to blindness and progressive sensorineural hearing loss 3. NDP mutations account for 8/81 cases in familial exudative vitreoretinopathy (FEVR) cohorts, predominantly presenting as advanced-stage disease with bilateral symmetry 4. Gene therapy delivering NDP cDNA via AAV9 successfully prevented cochlear pathology and restored retinal vascularization and visual function in disease models 3, establishing NDP as a promising therapeutic target. β-catenin stabilization alone in vascular endothelial cells is sufficient to rescue Norrie disease phenotypes 1, indicating the pathway's primacy in pathophysiology.