Lipid rafts are sphingolipid- and cholesterol-rich membrane microdomains that are insoluble in nonionic detergents. Lipid rafts are important for numerous cellular processes, including signal transduction, membrane trafficking and molecular sorting. Flotillins are lipid raft components in neurons and caveloae-associated proteins in A498 kidney cells. Flotillin-2, also designated epidermal surface antigen, is conserved in all mammalian species. Flotillin-1 and -2 have complementary tissue distributions and their expression levels are independently regulated. At the cellular level, Flotillin-2 is ubiquitously expressed, whereas Flotillin-1 is expressed in A498 kidney cells, muscle cell lines and fibroblasts. Stable transfection of a Flotillin-2 fusion protein in COS cells induces filopodia formation and changes epithelial cells to a neuronal appearance. Flotillins form a ternary complex with CAP and Cbl, directing the localization of the CAP-Cbl complex to a lipid raft subdomain of the plasma membrane. Association of ER-X with Flotillin localizes ER-X within plasma membrane caveloae and mediates rapid oestrogen activation of the MAP kinase cascade. The expression of the flotillins is also correlated to the progression of Alzhemier pathology.