Cholesterol transport between cellular membranes: A balancing act between interconnected lipid fluxes

Cholesterol represents the most abundant single lipid in mammalian cells. How its asymmetric distribution between subcellular membranes is achieved and maintained attracts considerable interest. One of the challenges is that cholesterol rarely is transported alone, but rather is coupled with heterotypic transport and metabolism of other lipids, in particular phosphoinositides, phosphatidylserine, and sphingolipids. This perspective summarizes the major exo- and endocytic cholesterol transport routes and how lipid transfer proteins at membrane contacts and membrane transport intersect along these routes. It discusses the co-transport of cholesterol with other lipids in mammalian cells and reviews emerging evidence related to the physiological relevance of this process. Cholesterol is the most abundant single lipid in mammalian cells. Ikonen and Zhou discuss major exo-and endocytic cholesterol transport routes and how lipid transfer proteins at membrane contacts and membrane transport intersect along these routes. They discuss co-transport of cholesterol with other lipids as well as physiological relevance.