Specific lipid self-associations in the fluid bilayer, particularly involving sphingolipids and cholesterol, are believed to result in the formation of membrane microdomains or “rafts” that mediate recycling of proteins between the cell surface and intracellular compartments or function as platforms for signal transduction events. Such membrane microdomains may be recovered in a low-density fraction that is insoluble in Triton X-100 at 4°C and referred to as detergent-insoluble, glycolipid-enriched complexes (DIGs). Membrane microdomains that constitute cell surface invaginations called caveolae can also be recovered in the form of DIGs. Caveolae are typically associated with a protein called caveolin, which coats their cytoplasmic surface.

Various glycosyl-phosphatidylinositol (GPI)-anchored proteins such as the folate receptor (FR) are believed to be associated with membrane rafts and to constitutively internalize and recycle to the cell surface although FR is the only known GPI-anchored protein with a transport function, i.e.,