Phosphoinositides regulate numerous cellular events via the recruitment and activation of multiple lipid-binding effector proteins. The precise temporal and spatial regulation of phosphoinositide signals by the co-ordinated activities of phosphoinositide kinases and phosphatases is essential for homeostasis and development. Mutations in two inositol polyphosphate 5-phosphatases, INPP5E and OCRL, cause the cerebrorenal syndromes of Joubert and Lowe s, respectively. INPP5E and OCRL exhibit overlapping phosphoinositide substrate specificity and subcellular localisation, including an association with the primary cilia. Here, we review recent studies that identify a new role for these enzymes in the regulation of primary cilia function. Joubert syndrome has been extensively linked to primary cilia defects, and Lowe s may represent a new class of ciliopathy associated syndromes.