Bestrophin 2 (BEST2) (BEST2)

Bestrophin 2 (BEST2) is a transmembrane protein that functions as a calcium-activated chloride channel (CaCC) and is also permeable to bicarbonate ions [UniProt: Q8NFU1]. It is a member of the bestrophin family, which is characterized by a highly conserved N-terminal region containing the channel pore. In humans, BEST2 is predominantly expressed in the non-pigmented epithelium of the ciliary body in the eye and in the goblet cells of the colon [PubMed: 18334555]. In the ocular setting, BEST2 is a key regulator of aqueous humor dynamics; its activity influences the rate of fluid secretion and, consequently, intraocular pressure (IOP) [PubMed: 21642533]. Research indicates that BEST2 deficiency or inhibition leads to significantly lower IOP, positioning it as a promising therapeutic target for the treatment of glaucoma and ocular hypertension [PubMed: 17652171]. In the digestive system, it contributes to bicarbonate-dependent mucus hydration and pH regulation [PubMed: 24451071]. While specific, high-affinity clinical drugs for BEST2 are still in the discovery phase, various small-molecule chloride channel blockers are used in experimental models to study its function. The development of selective BEST2 modulators remains a challenge due to the structural similarity between bestrophin isoforms, particularly BEST1, which is vital for retinal health.

Other names

Vitelliform macular dystrophy 2-like protein 1VMD2L1Bestrophin-2

Inhibition of calcium-activated chloride and bicarbonate transport to reduce aqueous humor production and lower intraocular pressure.