A protein complex that regulates PtdIns(3,5)P2 levels

Abstract

Phosphatidylinositol 3,5‐bisphosphate (PtdIns(3,5) P 2) is needed for retrograde membrane trafficking from lysosomal and late endosomal compartments and its synthesis is tightly regulated. But how cells regulate PtdIns(3,5) P 2 synthesis—for example, in response to hyperosmotic shock—remains unexplained. A paper from the Weisman group gives the most complete picture so far of a multiprotein complex that controls PtdIns(3,5) P 2 synthesis and explains how a VAC14 mutation functionally impairs the scaffold protein at the heart of the complex and causes a neurodegenerative condition in mice.