AbstractMembrane-boundphosphoinositidesaresignallingmoleculesthathaveakeyroleinvesicletraffickingineukaryoticcells1.Proteinsthatbindspecificphosphoinositidesmediateinteractionsbetweenmembrane-boundedcompartmentswhoseidentityispartiallyencodedbycytoplasmicphospholipidtags.Littleisknownaboutthelocalizationandregulationofmammalianphosphatidylinositol-3,5-bisphosphate（PtdIns（3,5）P2）,aphospholipidpresentinsmallquantitiesthatregulatesmembranetraffickingintheendosomeClysosomeaxisinyeast2.Herewedescribeamulti-organdisorderwithneuronaldegenerationinthecentralnervoussystem,peripheralneuronopathyanddilutedpigmentationinthe'paletremor'mouse.PositionalcloningidentifiedinsertionofETn2
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