Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling (By similarity). Involved in the organization of apical junctions in kidney cells together with NPHP1, NPHP4 and RPGRIP1L/NPHP8. Does not seem to be strictly required for ciliogenesis. Interacts with microtubules. Interacts with NPHP1. Interacts with DVL1, PRICKLE (PRICKLE1 or PRICKLE2) and Strabismus (VANGL1 or VANGL2) (By similarity). Binds calmodulin via its IQ domains. Interacts with APC2. Interacts with alpha-, beta-, and gamma-catenin. Interacts with N-cadherin (CDH2). Interacts with NPHP3 (By similarity). Interacts with IQCB1; the interaction likely requires additional interactors (By similarity). Component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme (By similarity). Associates with several components of the cytoskeleton including ciliary, random and polarized microtubules. During mitosis, it is recruited to mitotic spindle (By similarity). Membrane localization is dependent upon cell-cell contacts and is redistributed when cell adhesion is disrupted after incubation of the cell monolayer with low-calcium/EGTA medium. Also nuclear and perinuclear. Strongly expressed in the primary cilia of renal cells, especially in the varicosities, swellings observed in the cilia. Localizes in the node monocilia and in other 9+0 monocilia, including those of kidney epithelial cells and the pituitary gland, but it does not localize to 9+2 cilia (at protein level). In adult, it is expressed at high level in liver and kidney. Weakly or not expressed in other tissues. Expressed from 7 dpc. Expressed in presomite-stage embryos, before asymmetrical expression of Nodal and Lefty. The D-box 1 (destruction box 1) mediates the interaction with APC2, and may act as a recognition signal for degradation via the ubiquitin-proteasome pathway. May be ubiquitinated via its interaction with APC2. Hydroxylated at Asn-75, most probably by HIF1AN. Constant reversal of left/right polarity (situs inversus) and cyst formation in the kidneys. Exon 14b skipped. Exon 14a skipped. Exon 5 skipped. Exon 13 skipped. Exon 13 skipped with exon 14b.