APOE is an apolipoprotein, a protein associating with lipidparticles, that mainly functions in lipoprotein-mediated lipidtransport between organs via the plasma and interstitial fluids. APOE is a corecomponent of plasma lipoproteins and is involved in their production, conversion and clearance. Apoliproteins are amphipathic molecules that interactboth with lipids of the lipoprotein particle core and the aqueousenvironment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) andintermediate density lipoproteins (IDL) but shows a preferentialbinding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptorsincluding the LDL receptor/LDLR, the LDL receptor-related proteinsLRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLRthat mediate the cellular uptake of the APOE-containing lipoproteinparticles. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supportsthe capture and the receptor-mediated uptake of APOE-containinglipoproteins by cells. A main function of APOE is to mediate lipoproteinclearance through the uptake of chylomicrons, VLDLs, and HDLs byhepatocytes. APOE is also involved in thebiosynthesis by the liver of VLDLs as well as their uptake byperipheral tissues ensuring the delivery of triglycerides and energystorage in muscle, heart and adipose tissues. By participating in the lipoprotein-mediateddistribution of lipids among tissues, APOE plays a critical role inplasma and tissues lipid homeostasis. APOE is also involved in two steps of reversecholesterol transport, the HDLs-mediated transport of cholesterol fromperipheral tissues to the liver, and thereby plays an important role incholesterol homeostasis. First, it is functionally associated with ABCA1 inthe biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake byhepatocytes. APOE also plays an important role inlipid transport in the central nervous system, regulating neuronsurvival and sprouting. APOE is alsoinvolved in innate and adaptive immune responses, controlling forinstance the survival of myeloid-derived suppressor cells. Binds to the immune cell receptor LILRB4. APOE may also play a role in transcriptionregulation through a receptor-dependent and cholesterol-independentmechanism, that activates MAP3K12 and a non-canonical MAPK signaltransduction pathway that results in enhanced AP-1-mediatedtranscription of APP. [1-7]

MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH