Bestrophin-1 (BEST1) (BEST1)

Bestrophin-1 is a transmembrane protein encoded by the BEST1 gene that functions as a calcium-activated chloride channel (CaCC) located primarily in the basolateral membrane of the retinal pigment epithelium (RPE) [UniProt: P56645]. It plays a critical role in maintaining the ionic environment and fluid homeostasis of the subretinal space, which is essential for the health and survival of photoreceptor cells [PubMed: 30643209]. Mutations in the BEST1 gene lead to a group of inherited retinal degenerations known as bestrophinopathies, characterized by the accumulation of lipofuscin-like material and fluid beneath the macula, resulting in progressive vision loss [NCBI Gene: 7439, OMIM: 603785]. While no small-molecule drugs are currently approved for this target, BEST1 is a primary focus for gene therapy development, with candidates like ATSN-201 utilizing adeno-associated virus (AAV) vectors to deliver functional gene copies to the RPE [ClinicalTrials.gov: NCT05622721]. Research is also ongoing into pharmacological chaperones and CRISPR-based gene editing to address specific pathogenic variants that cause dominant-negative effects [PubMed: 31511310].

Other names

VMD2Vitelliform macular dystrophy 2 proteinTU15BBestrophin 1

Gene augmentation therapy via viral vectors to restore functional chloride channel activity in the retinal pigment epithelium; experimental small-molecule modulation of channel gating.