The inositol 5-phosphatases OCRL and INPP5B: Cellular functions and roles in disease.

OCRL and INPP5B are evolutionary conserved inositol 5-phosphatases that preferentially hydrolyse PI(4,5)P2, a key regulator of numerous cellular processes. Mutation of OCRL causes Lowe syndrome and Dent-2 disease that manifest in the eye, brain and kidney, whereas mutations in INPP5B have not been reported to cause disease. Here, we provide a current view of the biology of both proteins, describing their subcellular locations, interaction partners and cellular processes they mediate or that are sensitive to their loss of function. There are many similarities in these properties between OCRL and INPP5B, albeit with some important differences. We also discuss the mechanisms underlying Lowe syndrome and Dent-2 disease, and the possible influence of INPP5B in dictating final phenotypic outcome. The knowledge gained studying OCRL and INPP5B has improved understanding of how cells function and will inform the design of new treatments for Lowe syndrome and Dent-2 disease and possibly other conditions.