Nphp1, encoding nephrocystin-1, is a gene of great significance. The protein functions at the transition zone of primary cilia and is crucial for normal ciliary-dependent signaling. Mutations in Nphp1 are associated with ciliopathies, especially nephronophthisis, a tubulointerstitial kidney disorder that often leads to end-stage renal failure [1,4].

An Nphp1 knockout mouse model targeting exon 2-20 was created to study its functions [2]. These Nphp1del2-20/del2-20 mice faithfully reproduced the renal and extrarenal phenotypes of human nephronophthisis, including renal cyst development, tubular basement membrane thickening, retinal degeneration, and abnormal spermatogenesis. Re-expression of Nphp1 using an adenoviral-associated-virus-9 vector could partially rescue both renal and retinal phenotypes in these mice. In addition, patients with Nphp1-associated nephronophthisis often have an occult retinopathy, with a mild retinal phenotype mainly affecting cones, and advanced retinal degeneration may occur with aging [3].

In conclusion, Nphp1 is essential for maintaining normal ciliary function and is closely related to the development of nephronophthisis and associated retinal disorders. The Nphp1 knockout mouse model provides a valuable tool for studying the gene's function and developing novel treatments for these childhood-onset diseases.