Renal fibrosis is an inevitable outcome of end-stage chronic kidney disease. During this process, epithelial cells lose E-cadherin expression. -Catenin may act as a mediator by accumulation and translocation to the nucleus. Studies have suggested that CIP4, a Cdc42 effector protein, is associated with -catenin. However, whether CIP4 contributes to E-cadherin loss in epithelial cells by regulating -catenin translocation is unclear. In this study, we investigated the involvement of CIP4 in -catenin translocation. Expression of CIP4 was upregulated in renal tissues of 5/6 nephrectomized rats and mainly distributed in renal tubular epithelia. In TGF-1-treated NRK-52E cells, upregulation of CIP4 expression was accompanied by reduced expression of E-cadherin. CIP4 overexpression promoted the translocation of -catenin to the nucleus, which was accompanied by reduced expression of E-cadherin even without TGF-1 stimulation. In contrast, CIP4 depletion by using siRNA inhibited the translocation of -catenin to the nucleus and reversed the decrease in expression of E-cadherin. The interaction between CIP4 and -catenin was detected. We also show that -catenin depletion could restore the expression of E-cadherin that was suppressed by CIP4 overexpression. In conclusion, these results suggest that CIP4 overexpression represses E-cadherin expression by promoting -catenin translocation to the nucleus.