Nephronophthisis-type 2 (NPHP2) is an infantile renal disease whose features include: tubular basement membrane disruption, renal interstitial fibrosis, enlarged kidneys and widespread renal cyst development (Otto et al. 2003). Occasionally, reversal of the left-right body plan (situs inversus) also occurs. NPHP2 is caused by a mutation of the INVS gene located on human chromosome 9q21–q22 (Otto et al. 2003). In the mouse, deletion of exons 3–11 of the Invs gene also causes a phenotype of cystic kidneys and situs inversus. Detailed anatomical studies of the inv -/- mouse kidney have confirmed that it is a good model for the early stages of human NPHP2 (Phillips et al. 2004). The protein encoded by the INVS (human) and Invs (mouse) genes is called inversin (for a review see Eley et al. 2004). The full length murine protein contains 1062 amino acids, but shorter isoforms with 924 and 897 amino acids have been identified. Analysis of the human INVS gene sequence suggests that the human and mouse inversin proteins are very similar (Eley et al. 2004). Inversin is expressed in the plasma membrane and junctional complexes of renal epithelia, and is highly expressed in the primary cilium on renal cells. Many human and murine proteins, whose mutation is associated with renal cyst formation and, in some cases laterality defects, are also expressed in the primary cilium. Therefore, establishing inversin’s function in the primary cilium is probably the key to understanding why humans with NPHP2 and inv -/- mice develop renal cysts. Renal cyst formation probably involves both abnormal morphogenesis and enhanced secretory activity by the tubular epithelium. Inversin expressed in the primary cilium may affect morphogenesis by acting as a flow-regulated molecular switch between canonical and noncanonical Wnt signalling pathways, which regulate a diverse range of developmental processes (Simons et al. 2005). The noncanonical Wnt pathway may be important for correct development of the renal tubules and for the maintenance of correct cell orientations in developed tubules. In the absence of inversin, the canonical Wnt signalling pathway operates unabated, leading to the cystic phenotype characteristic of NPHP2 and the inv -/- mouse (Germino 2005; Simons et al. 2005). Our work is concerned with the secretory aspects of cyst formation. The purposes of this study were: (i) to establish whether secretory Cl^– channels (CFTR and Ca²⁺-activated Cl^– channels) were upregulated in inv -/- cells, and (ii) to test whether Ca²⁺ signalling, including cilium-mediated Ca²⁺ signalling, was abnormal in the renal cells of inv -/- mice. Renal collecting ducts were isolated from wild type (+/+), heterozygote (+/-) and homozygous inv (-/-) mice and used to produce primary cultures of renal collecting duct cells. Most of the cultured cells possessed a primary cilium, which was clearly visible using differential interference contrast optics. It was possible to bend the cilium on a single cultured cell using either positive or negative pressure applied via a micropipette. The results of experiments in which we measured whole cell Cl^– currents and global changes in [Ca²⁺]_i following application of agonists and bending of the primary cilium will be discussed.