Bestrophins were first found by genetic linkage of human-Bestrophin-1 (hBest1) to a juvenile form of macular degeneration called Best vitelliform macular dystrophy. To date Bestrophin 1-4 have been identified, although Bestrophin-3 and Bestrophin-4 have been observed only at the RNA level. In addition, splice variants of some of these Ca2+-activated Cl– channels (CaCCs) have also been detected. CaCCs are known to be involved in the regulation of olfaction, taste, phototransduction, and excitability in the nervous system. However, the molecular identity and functional role of CaCC in the brain have not been well established.