Apolipoprotein E (Apo E) is a class of lipoproteins found in chylomicrons and intermediate-density lipoproteins. It is essential for the normal metabolism of lipoprotein components rich in triglycerides. In peripheral tissues, Apo E is primarily produced by the liver and macrophages, mediating isoform-dependent cholesterol metabolism. In the central nervous system, Apo E is mainly produced by astrocytes and can transport cholesterol to neurons through Apo E receptors. Apo E transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymphatic system and then into the blood. In the field of immune regulation, increasing evidence suggests that Apo E interacts with many immune processes, including inhibiting T cell proliferation, regulating macrophage function, promoting lipid antigen presentation to natural killer T cells, and modulating inflammation and oxidation. Apo E secreted by monocytes is downregulated by inflammatory cytokines and upregulated by TGF-β. This protein is involved in Alzheimer’s disease and cardiovascular diseases.