Together, our data indicate that Inpp5e functions as a key regulator of cell polarity in the renal epithelia, by inhibiting PtdIns(3,4,5)P<sub>3</sub> and subsequently stabilizing PtdIns(4,5)P<sub>2</sub> and recruiting Ezrin, F-actin, and basal bodies to the apical membrane, and suggest a possible novel approach for treating human ciliopathies.