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Significance Membrane lipid homeostasis within cells requires a cooperation of vesicular transport and of lipid transfer proteins that mediate lipid exchange between membranes independent of bilayer fusion. Many such proteins also function as tethers connecting adjacent bilayers. For membranes that travel along the exo- and endocytic pathways, these tethers must be regulated to ensure their action selectively at specific stations of their journey. Here we identify a mechanism that recruits the endoplasmic reticulum (ER) to late endosomes/lysosomes and that may promote exchange of lipids between their membranes. These contacts rely on the binding of an ER-anchored lipid transfer protein to a key player in endosomal maturation, the small GTPase Rab7, thus explaining how their formation is regulated in time and space.

PDZD8 mediates a Rab7-dependent interaction of the ER with late endosomes and lysosomes