Mammalian Cl^- channels can be broadly classified into four different families: voltage-dependent Cl^- channels (CLCs), the cystic fibrosis transmembrane conductance regulator (CFTR), ligand-gated Cl^- channels (γ-aminobutyric acid (GABA)) and glycine channels) and Ca²⁺-activated Cl^- channels (Bestrophin and Anoctamin channels).

Bestrophins were first found by genetic linkage of human-Bestrophin-1 (hBest1) to a juvenile form of macular degeneration called Best vitelliform macular dystrophy^1,2. To date Bestrophin 1-4 have been identified, although Bestrophin-3 and Bestrophin-4 have been observed only at the RNA level³. In addition, splice variants of some of these Ca²⁺-activated Cl^- channels (CaCCs) have also been detected^2,4,5. 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 established⁶. Bestrophin-2 is prominently expressed in colon and testes. Recently, Bestrophin-2 has also been found to be expressed in olfactory sensory neurons (OSNs)⁷.

Two different topologies for Bestrophin-1 have been proposed. The first structure proposes that six hydrophobic domains span the membrane⁸, while the second suggests that there are only four membrane-spanning domains⁹. The same structural controversy applies to Bestrophin-2. Bestrophin-1 and Bestrophin-2 (as well as Bestrophin-4 by heterologous expression) are activated by intracellular Ca^{2+ 10-12}. Ca²⁺-dependent activation of Bestrophin-2 was also demonstrated in Xenopus¹³.