Nphp1, associated with nephronophthisis, encodes nephrocystin-1, a protein functioning at the transition zone of primary cilia. Primary cilia are crucial for tissue development and signal transduction, and mutations in ciliary-associated proteins lead to ciliopathies. Nphp1 is significant as mutations in it are a common cause of nephronophthisis, a tubulointerstitial kidney disorder often resulting in end-stage renal failure [1,2,4].

A knockout mouse model targeting exon 2-20 of Nphp1 (Nphp1del2-20/del2-20) recapitulated 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 the renal and retinal phenotypes in these mice, making it a valuable model for studying Nphp1 function and developing treatments [3].

In conclusion, Nphp1 is essential for normal function of primary cilia, especially in the context of nephronophthisis. The Nphp1 knockout mouse model has been instrumental in revealing its role in renal and extrarenal phenotypes related to this disease, facilitating a better understanding of the underlying mechanisms and potentially guiding the development of novel therapies.