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Lowe syndrome is characterized by congenital cataracts, renal proximal tubule dysfunction, cognitive disabilities and developmental delay (Delleman et al., 1977; Kenworthy and Charnas, 1995; Böckenhauer et al., 2008).

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SNX9, an adaptor that couples late-stage endocytic coated pits to actin polymerization and which we found to bind OCRL directly, remains associated with such vesicles.The broad intracellular localization of OCRL may reflect its importance in preventing the build-up of ectopic intracellular pools of PI(4,5)P.Alternatively, OCRL may act on small yet physiologically relevant pools of these phosphoinositides on intracellular membranes.The human genome contains 10 genes encoding inositol 5-phosphatases, a group of enzymes that dephosphorylate the inositol ring at the 5 position, nine of which act on inositol phospholipids (Dyson et al., 2012; Pirruccello and De Camilli, 2012).Mutations in one such gene, OCRL, give rise to Oculo-Cerebro-Renal syndrome of Lowe (Lowe syndrome) and type 2 Dent's disease, two X-linked diseases (Attree et al., 1992; Hoopes et al., 2005).

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