Cholesterol in health and disease

Imagine if an excess amount of a critical, life-sustaining molecule like ATP were, by a perverse series of events involving the lifestyle of modern humans, causally related to a major human disease.The thought of "ATP" being synonymous with poor health and poor living in the minds of the lay public and press, even of health care providers, would be difficult for any selfrespecting scientist to accept.So one might view the biomedical history of cholesterol -indeed, this history might be seen as even stranger than the hypothetical ATP scenario, given that evolution has devoted close to 100 genes to the synthesis, transport, metabolism, and regulation of cholesterol.This structurally fascinating lipid is utterly essential to the proper functioning of cells and organisms.Cholesterol, cholesterol metabolites, and immediate biosynthetic precursors of cholesterol play essential roles in cellular membrane physiology, dietary nutrient absorption, reproductive biology, stress responses, salt and water balance, and calcium metabolism.Indeed, many of the articles in this Perspective series are devoted to the normal physiology of cholesterol.Still, there is little doubt that the disease process responsible for the leading cause of death in the industrialized world -atherosclerosis -is a disorder in which an excess of cholesterol is a major culprit.How did evolution come up with a molecule that is critical for so many aspects of normal physiology, and what went "wrong"? Cholesterol in health and disease