Loss of the phosphoinositide 5-phosphatase OCRL causes accumulation of PtdIns(4,5)P2 on membranes and, ultimately, Lowe syndrome. In this issue, Mondin et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201805155) discover that a surprising partnership between PTEN and the phospholipase PLCXD can compensate for OCRL to suppress endosomal PtdIns(4,5)P2 accumulation.
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