Bestrophin-1 (Best1) anion channel; VMD2 gene product (NO₃^- > I^- > Br^- > Cl^-; P_NO3^-/P_Cl^- = 5.8) (Sun et al., 2002). Regulated by ceramide-induced dephosphorylation (Xiao et al., 2009).  Best1 mediates fast and slow glutamate release in astrocytes upon GPCR activation (Woo et al. 2012).  Progressive posterior chorioretinal changes occur over time in the initial ADVIRC proband, leading to visual loss. The causative mutation is in the transmembrane domain of BEST1 (Chen et al. 2016).  Autosomal dominant vitreoretinochoroidopathy (ADVIRC), caused by mutation in BEST-1, is a rare, early-onset retinal dystrophy characterised by distinct bands of circumferential pigmentary degeneration in the peripheral retina accompanied by developmental eye defects. It is an ion channel in the basolateral membrane of retinal pigment epithelial (RPE) cells. In patients, BEST1 is expressed at the basolateral membrane and the apical membrane. PolarProtPred is a program for predicting apical and basolateral localization of transmembrane proteins using putative short linear motifs and deep learning (Dobson et al. 2021). During human eye development, BEST1 is expressed more abundantly in peripheral RPE compared to central RPE and is also expressed in cells of the developing retina. Higher levels of mislocalised BEST1 expression in the periphery, from an early developmental stage, may provide the mechanism that leads to the distinct clinical phenotype observed in ADVIRC patients (Carter et al. 2016).  Binding of Ca²⁺ induces conformational changes in the secondary structure leading to assembly of monomers and changes in molecular and macro-organization (Mladenova et al. 2016). BEST1 gene mutations are associated with at least two different forms of macular dystrophy (Chibani et al. 2019). intermolecular protein-lipid interactions may account for the conformational dynamics of hBest1 and its biological function as a multimeric ion channel (Videv et al. 2021). hBest1 is expressed in the retinal pigment epithelium, and mutations in the BEST1 gene cause ocular degenerative diseases colectivelly referred to as "bestrophinopathies". Videv et al. 2021 reviewed the current understanding of hBest1 surface organization, interactions with membrane lipids in model membranes, and its association with microdomains of cellular membranes. Shifts in phase separation/miscibility by cholesterol leads to changes in the structure and localization of hBest1 in the lipid rafts and its channel functions (Videv et al. 2022).