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Concomitantly, LDLR ubiquitylation is increased but its degradation is reduced and ESCRT (Endosomal sorting complex required for transport) proteins are downregulated. Co-depletion of IDOL (Inducible degrader of the LDLR), which ubiquitylates the LDLR and promotes its degradation, rescues PM LDLR levels and LDL uptake. In oligodendrocytes, Ndrg1 silencing not only results in reduced LDL uptake but also downregulation of the oligodendrocyte differentiation factor Olig2. Both phenotypes are rescued by co-silencing of Idol, suggesting that ligand uptake via LDLR family members controls oligodendrocyte differentiation. These findings identify NDRG1 as a novel regulator of multivesicular body formation and endosomal LDLR trafficking. 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