A major hurdle for organisms to dispose of cholesterol is the inability to degrade the sterol nucleus which constitutes the central part of the molecule. Synthesis of the sterol nucleus requires a complex, energy costly, metabolic pathway but also generates a diverse array of intermediates serving crucial roles in cellular energy metabolism and signal transduction. This may be the reason why this complex pathway has survived evolutionary pressure. The only way to get rid of substantial amounts of cholesterol is conversion into bile acid or direct excretion of the sterol in the feces. The lack of versatility in disposal mechanisms causes a lack of flexibility to regulate cholesterol homeostasis which may underlie the considerable human patho...