Lipoprotein(a) [Lp(a)] is an enigmatic lipoprotein particle present in the plasma from humans, great apes and hedgehogs. Plasma levels of Lp(a) vary widely between individuals and are largely determined by specific sequences within the gene encoding apo(a), the unique highly polymorphic glycoprotein attached to apoB of low density lipoprotein (LDL) to form Lp(a). Elevated plasma concentrations of LP(a) are associated with the premature development of atherosclerosis. A major goal of our laboratory is to better understand the metabolism of Lp(a) and its function in humans. We have identified unexpected and large variations in plasma Lp(a) levels during renal disease, HIV-infection and in sepsis. Moreover, we have observed an association between Lp(a) and Alzheimer disease. Taken together, our observations suggest that Lp(a) may constitute a novel target in our fight against cardiovascular and neurodegenerative disorders.