NPHP1 (nephrocystin 1) is a ciliary protein essential for kidney function and retinal development. It localizes to the ciliary transition zone and functions in organizing apical junctions in kidney cells alongside NPHP4 and RPGRIP1L 1. NPHP1 regulates intraflagellar transport (IFT) during cilia assembly, influencing movement of IFT proteins like IFT88, and plays roles in cell polarity control and signal transduction through recruitment of PTK2B/PYK2 to cell-matrix adhesions 2. Mutations in NPHP1 cause nephronophthisis (NPH), an autosomal recessive ciliopathy characterized by progressive tubulointerstitial nephritis and kidney failure 3. NPHP1 mutations represent the most frequent genetic cause, accounting for approximately 53% of NPH cases in large cohorts 4. Clinical severity varies by mutation type: NPHP1 patients typically progress to end-stage renal disease at median age 13.5 years, with growth retardation and hypertension as independent factors accelerating kidney failure 5. NPHP1 mutations are also associated with Joubert syndrome (requiring renal function monitoring) and Senior-Loken syndrome (retinitis pigmentosa with renal involvement) 6. NPHP1 mutations have been identified in macular and cone/cone-rod dystrophies, highlighting retinal involvement 7. Understanding NPHP1 pathomechanisms involving ciliary dysfunction and planar cell polarity defects is crucial for developing therapeutic interventions.