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The primary cilium (PC) is a plasma membrane-derived structure of great importance for cell and organismal physiology. Indeed, abnormalities in assembly or function of the PC trigger the onset of a group of genetic diseases collectively known as ciliopathies. In recent years, it has become evident that the integrity and function of the PC depends substantially on signaling elements such as phosphoinositides (PI) and their regulators. Because phospholipids such as PI(4,5)P 2 constitute recruitment platforms for cytoskeleton, signaling, and trafficking machinery, control over their levels is critical for PC function. Although information about phosphoinositol phosphate (PIP) kinases in the PC is scarce, a growing body of evidence sup- ports a role for PIP phosphatases in cilia assembly/maintenance. Indeed, deficiencies in two 5' PIP phosphatases, Inpp5E and Ocrl1, are clearly linked to ciliopathies like Joubert/MORM syndromes, or ciliopathy-associated dise ases like Lowe syndrome. Here, we review the unique roles of these proteins and their specific site of action for ensuring ciliary integrity. Further, we discuss the possibility that a phosphatase relay system able to pass PI control from a preciliary

Role of Ocrl1 and Inpp5E in primary cilia assembly and maintenance: a phosphatidylinositol phosphatase relay system?