Mutations in WNK4 have been linked to hypertension in PHAII. Paracellular ion transport has been reported to be involved in this disease process; however, the specific molecular target has not been identified. In this study, we found that TJ protein claudin‐7 and WNK4 were partially co‐localized in renal tubules of rat kidney and co‐immunoprecipitated in kidney epithelial cells. The wild‐type and PHAII‐causing mutant, but not the kinase‐dead mutant, phosphorylated claudin‐7. We have identified ser206 in the COOH‐terminus of claudin‐7 as a putative phosphorylation site for WNK4. More importantly, disease‐causing mutant enhanced claudin‐7 phosphorylation and significantly increased paracellular permeability to Cl−.