Human apolipoprotein E (apoE) is a 299-residue polymorphic protein (Mr =34 kDa).It is composed of two independently folded domains that are separated by a hinge region.The 22-kDa N-terminal domain (residues 1-191) and the 10-kDa C-terminal domain (residues 216-299) of apoE are responsible for receptor binding and lipid binding,respectively.The APOE gene has three major alleles,ε2,e3 and ε4,which encode three major isoforms,apoE2,apoE3,and apoE4,respectively.The three isoforms differ from one another only at residue 112 and 158,but have marked differences in their biological functions.ApoE has been known to play a key role in the transport of plasma cholesterol and lipoprotein metabolism.The lipid-and receptor-binding abilities of apoE are isoform-specific.Besides,apoE is also highly associated with late-onset familial and sporadic Alzheimers disease (AD).The allele ε4 is a risk factor for Alzheimers disease.The structural characteristics of apoE isoforms may play important roles in their biological functions.