Ca²⁺ acivated Cl^- channels (CaCC) have fundamental importance in most tissues. Recently identified ANO1 (TMEM16A) is an intrinsic constituent of CaCC in cultured epithelia and loss of ANO1 causes a defect in epithelial Ca²⁺-dependent chloride transport in knockout (ko) mice. However, the physiological significance of ANO1 in kidneys is unknown. TMEM16 family comprises 10 protein members some of them are broadly expressed in different organs, like ANO6. RT-PCR analysis shows that ANO1 and ANO6 are expressed in mouse kidney, namely in podocytes and in proximal tubule. Furthermore we detected ANO1 and ANO6 expression in human glomeruli. Immunofluorescence staining of ANO1 in mouse and human kidney revealed an apical expression in the proximal tubule cells where it co-localizes with cubulin, but not with calbindin, a distal convoluted tubule marker. ANO1 expression shows no co-localization with the collecting duct marker, AQP2. In contrast, ANO6 appears to have a basolateral expression and doesn't co-localize with cubilin in the proximal tubule. Urine samples from wt- and ANO1-ko mice revealed a high molecular weight proteinuria and electromycroscopy analysis of wt- and ANO1-ko kidney slices showed changes in the morphology of glomerular podocytes and accumulation of intracellular vesicles in the proximal tubular cells. However, as reported earlier, ANO1-ko leads to death within one week in most cases, which compromises the phenotype analysis in adult mice. To this end we are developing conditional ANO1-ko mice by crossing a floxed ANO1 mice with a podocyte specific Cre mice. Supported by DFG, SFB699, DF: PhD fellowship SFRH/BD/43313/2008