Human Apolipoprotein E (APOE) Protein

Background

Apolipoprotein E (APOE) is a critical glycoprotein involved in lipid metabolism, lipid transport, and cholesterol homeostasis. ApoE is synthesized primarily in the liver, brain, and adipose tissue and is a major component of chylomicron remnants, VLDL, and HDL particles. It facilitates the clearance of triglyceride-rich lipoproteins by binding to specific receptors, including the low-density lipoprotein receptor (LDLR) and LRP1, enabling lipoprotein uptake in the liver. ApoE plays a significant role in reverse cholesterol transport, promoting the efflux of cholesterol from peripheral tissues to the liver for excretion. ApoE exists in three common isoforms – ApoE2, ApoE3, and ApoE4 – which influence lipid metabolism and disease risk. The ApoE4 allele is a major genetic risk factor for Alzheimer’s disease, as it impairs beta-amyloid clearance and exacerbates neurodegeneration. ApoE is also implicated in atherosclerosis, cardiovascular disease, and type 2 diabetes due to its role in lipid transport and inflammation. ApoE regulates immune function and inflammatory responses, contributing to tissue repair and maintenance. Therapeutic strategies targeting ApoE pathways, such as receptor modulators and lipid-lowering therapies, are under investigation for their potential in treating neurodegenerative and cardiovascular diseases. ApoE’s pleiotropic effects on lipid metabolism, brain health, and immune regulation underscore its importance as a key protein in human physiology.