NPHP3 encodes nephrocystin-3, a ciliary protein essential for normal kidney development and function. The protein localizes to the ciliary compartment and interacts with other nephrocystin family members to regulate ciliary structure and signaling 1. NPHP3 functions as a molecular switch controlling Wnt signaling pathways, specifically inhibiting disheveled-1-induced canonical Wnt signaling while regulating non-canonical planar cell polarity pathways required for convergent extension and left-right axis determination 2. NPHP3 mutations cause nephronophthisis-3 (NPH3), characterized by early-onset cystic kidney disease with a median ESKD onset of 4.0 years—significantly earlier than other NPH types 3. Biallelic NPHP3 variants also cause renal-hepatic-pancreatic dysplasia-1 (RHPD1), a severe neonatal condition affecting multiple organ systems 4. NPHP3 mutations represent a substantial proportion of infantile NPH cases, particularly in East Asian populations, with liver involvement observed in all affected patients 5. Senior-Loken syndrome patients with NPHP3 variants typically present with nephropathy rather than early retinopathy 6. Clinical management requires early intervention for kidney disease monitoring, with variant type influencing disease progression 3.