Nephrocystin-1 (NPHP1)

Nephrocystin-1 is a protein encoded by the NPHP1 gene that localizes primarily to the base of cilia in renal, respiratory, and retinal cells, where it is involved in the organization of cell-cell and cell-matrix junctions, regulation of epithelial cell polarity, and maintenance of ciliary structure and function[1][2][3][5]. Structurally, it contains a Src homology 3 (SH3) domain and other conserved domains that facilitate protein-protein interactions—especially with actin-binding proteins like filamin—and help coordinate cytoskeletal organization at cell junctions[2][3][5]. Loss-of-function mutations in NPHP1 lead to juvenile nephronophthisis, a hereditary cystic kidney disease of childhood marked by tubular atrophy and interstitial fibrosis, often progressing to end-stage renal disease, and can also cause syndromic ciliopathies including Senior-Løken syndrome (kidney and retinal degeneration) and Joubert syndrome (multisystem involvement)[1][2]. Nephrocystin-1 is not currently considered a direct therapeutic target—there are no drugs known to interact with it, and no established safety concerns arising from its pharmacologic modulation[1][2]. Its gene status may, however, be used as a diagnostic marker for hereditary nephronophthisis[1].

Other names

juvenile nephronophthisis 1 proteinnephronophthisis 1 (juvenile)NPH1SLSN1JBTS4NPHP1 protein, human