Cell organelles and the plasma membrane have unique lipid compositions. Consequently, there is a gradient of lipid-dependent properties along the secretory pathway. We focus here on the steep sterol gradients that exist between the endoplasmic reticulum and plasma membrane, as well as across the plasma membrane where sterols are found principally in the cytoplasmic leaflet. Recent progress in these areas has been remarkable, with new concepts and molecules to account for non-vesicular intracellular sterol transport, and an exciting new mechanism to explain the unexpected transbilayer distribution of sterols.
