Bestrophin-2 (BEST2)

Bestrophin-2 (BEST2) is a member of the bestrophin family of **calcium-activated anion channels**, functioning primarily as a chloride channel and more recently recognized for its ability to mediate the efflux of glutamate and glutamine in a calcium-dependent manner[2][3][1]. BEST2 is mainly expressed in the **non-pigmented ciliary epithelium of the eye** and the colon[1][3]. Structurally, BEST2 assembles as a pentameric transmembrane channel, with critical gating and ion selectivity roles determined by specific amino acid residues, especially in the second transmembrane domain and a unique C-terminal auto-inhibitory segment[2][5][7]. In the eye, BEST2 contributes to the **regulation of intra-ocular pressure**, with knockout studies indicating its involvement in aqueous humor dynamics[3][5]. BEST2 also physically interacts with **glutamine synthetase (GS)**, forming a complex that regulates both glutamate metabolism and its transmembrane transport, revealing a unique mechanism for local neurotransmitter/glutamate signaling control[3]. Although BEST2 dysfunction is not directly linked to a specific inherited disease in humans, its functional relevance in ocular physiology and possible roles in glutamate cytotoxicity under hypertensive conditions in the eye suggest potential pathological significance[3][5]. There are **no established drugs targeting BEST2 as a therapeutic target** to date, nor are there validated biomarkers or direct human disease associations for patient selection[3][5]. Because of its signaling and metabolic functions, potential safety and toxicological concerns may center on altered glutamate handling in the eye[3]. Key literature highlights: - BEST2 forms a calcium-activated chloride channel essential for anion homeostasis in ocular tissues[2][5][7]. - Uniquely, it interacts with glutamine synthetase to regulate glutamate disposition, linking ionic conductance with neurotransmitter metabolism[3]. - Structural differences from the related Bestrophin-1 determine its functional specificity and ion selectivity[2][7].

Other names

Bestrophin-2aVMD2L1FLJ20132Vitelliform macular dystrophy 2-like protein 1vitelliform macular dystrophy 2-like 1vitelliform macular dystrophy 2-like protein 1bestrophin-2aVMD2-like gene 1

Not established for approved or investigational drugs; modulates chloride/glutamate movement in response to intracellular calcium and glutamate concentrations