INVS (inversin) is a ciliary protein essential for normal renal development and left-right axis establishment. It functions as a molecular switch regulating Wnt signaling by inhibiting the canonical pathway through targeting cytoplasmic disheveled (DVL1) for proteasomal degradation, thereby permitting terminal differentiation of tubular epithelial cells. INVS localizes to the ciliary inversin compartment and cooperates with NPHP1, NPHP4, and RPGRIP1L/NPHP8 in organizing apical junctions in kidney cells, though it is not strictly required for ciliogenesis itself. Pathogenic INVS variants cause nephronophthisis 2 (NPHP2), an autosomal-recessive ciliopathy characterized by progressive cystic kidney disease 1. INVS mutations represent a notable subset of nephronophthisis-related ciliopathies, with clinical phenotypes that may present atypically; some patients with truncating INVS mutations exhibited delayed disease onset without typical infantile presentation or extrarenal manifestations 1. In Senior-Loken syndrome (characterized by retinopathy and nephronophthisis), INVS variants are associated with later-onset retinopathy compared to CEP290 or IQCB1 mutations, with nephropathy developing as a primary manifestation 2. Recent exome sequencing studies identified novel INVS variants in fetuses with structural anomalies and critically ill pediatric patients, expanding the recognized mutation spectrum 3 4.