Nephrocystin-1 (NPHP1) (NPHP1)

Nephrocystin-1 (NPHP1) is a scaffolding protein localized to the transition zone of primary cilia and the connecting cilium of retinal photoreceptors (UniProt: O15259). It functions as part of a protein complex that regulates ciliary protein trafficking and maintains the structural integrity of the ciliary gate, which is essential for the survival of light-sensing cells (PubMed: 21515823). Mutations in the NPHP1 gene lead to ciliopathies such as nephronophthisis and Senior-Løken syndrome, the latter of which is characterized by progressive renal failure and retinal degeneration (NCBI Gene: 4867). In retinal cells, the loss of Nephrocystin-1 disrupts the transport of opsins and other critical proteins, leading to photoreceptor cell death and blindness. As a therapeutic target, NPHP1 is the focus of gene augmentation strategies using adeno-associated viral (AAV) vectors to restore protein expression and halt disease progression (PubMed: 30103458). There are currently no approved small-molecule drugs for this target, making genetic intervention the primary clinical focus for treating NPHP1-related retinal dystrophy.

Other names

NephrocystinNPHP1JBTS4SLSN1Nephrocystin-1

Gene augmentation therapy to restore functional Nephrocystin-1 protein levels in the ciliary transition zone.