Apolipoprotein E plays a key protective role in atherosclerosis. Its capacity to safeguard against this disease can be attributed to at least three distinct functions. First, plasma apolipoprotein E maintains overall plasma cholesterol homeostasis by facilitating efficient hepatic uptake of lipoprotein remnants. Second, lesion apolipoprotein E in concert with apolipoprotein AI facilitates cellular cholesterol efflux from macrophage foam cells within the intima of the lesion. Third, lesion apolipoprotein E directly modifies both macrophage-and T lymphocyte-mediated immune responses that contribute to this chronic inflammatory disease.