Oligodendrocyte progenitor cells (OPCs) are found throughout the adult central nervous system (CNS), where they continually differentiate to produce new myelinating oligodendrocytes. This feature of OPCs makes them an attractive cellular target for enhancing remyelination and treating demyelinating diseases such as Multiple Sclerosis, however, a greater understanding of how OPCs respond to their environment is required to ensure this population is properly mobilised for repair. The low-density lipoprotein receptor related protein (LRP1), a large cell surface receptor and member of the low-density lipoprotein receptor family, is highly expressed by OPCs and downregulated during oligodendrocyte differentiation. By conditionally deleting Lrp1 from OPCs, we determined that LRP1 acts as a negative regulator of oligodendrocyte production in the adult mouse cortex and corpus callosum, but does not influence the myelinating profile of individual newborn oligodendrocytes. Furthermore, following cuprizone-induced demyelination, LRP1 expression by OPCs suppresses remyelination by influencing both the inflammatory response of OPCs as well as their differentiation into myelinating oligodendrocytes.