Myotubularin related protein 2 (MTMR2) is a member of the myotubularin family of 
phosphoinositide lipid phosphatases. Although MTMR2 dephosphorylates the 
phosphoinositides PI(3)P and PI(3,5)P2, the phosphoinositide binding proteins 
that are regulated by MTMR2 are poorly characterized. In this study, 
phosphoinositide affinity chromatography coupled to mass spectrometry identified 
receptor mediated endocytosis 8 (RME-8) as a novel PI(3)P binding protein. RME-8 
co-localized with the PI(3)P marker DsRed-FYVE, while the N-terminal region of 
RME-8 is required for PI(3)P and PI(3,5)P(2) binding in vitro. Depletion of 
PI(3)P by MTMR2 S58A or wortmannin treatment attenuated RME-8 endosomal 
localization and co-localization with EGFR on early endosomes. Our results 
suggest a model in which the localization of RME-8 to endosomal compartments is 
spatially mediated by PI(3)P binding and temporally regulated by MTMR2 activity.