Bestrophin-1 (BEST1)

Bestrophin-1 is an integral membrane protein encoded by the BEST1 gene, best known as a calcium-activated chloride channel primarily located in the basolateral membrane of retinal pigment epithelium (RPE) cells[1][2][3][4][5][6][7]. It regulates the flow of chloride ions in response to intracellular calcium, crucial for retinal ionic balance, photoreceptor health, and visual function[1][3][7]. Bestrophin-1 can also mediate neurotransmitter (glutamate, GABA) release in the brain, modulating synaptic activity under both physiological and pathological states (e.g., neuroinflammation)[4]. Mutations in BEST1 underlie several inherited retinal degenerations, collectively termed bestrophinopathies, including Best vitelliform macular dystrophy and other dystrophic or degenerative diseases of the retina[2][3][4]. There are currently no approved drugs that directly target Bestrophin-1, but its pathogenic role in eye diseases makes it a research target for genetic diagnosis and therapy[3][4][7]. The principal therapeutic and safety concerns relate to potential impacts on retinal function and vision if pharmacologically modulated.

Other names

Best1Vitelliform macular dystrophy protein 2VMD2

Calcium-activated gating of chloride channel, Permits chloride (and, in some tissues, glutamate and GABA) flux across membranes, Channel opening modulated by calcium binding and C-terminal auto-inhibitory segment