Bestrophin-1 (BEST1) in the Central Nervous System from Mechanism to Disease

Bestrophin-1 (BEST1) was first linked to retinal disease, yet in the central nervous system BEST1 has been assigned a distinct functional scope spanning transmitter permeation, circuit set point control, and injury responses. In this mini-review, current evidence is examined for BEST1 as a neurotransmitter-gated anion channel, with emphasis placed on structural and biophysical studies that have clarified gating, pore behavior, and ligand-dependent tuning. The long-running dispute over CNS localization is critically revisited, because broad conclusions have often rested on antibodies lacking stringent validation. Astrocytic BEST1 is then considered in the setting of tonic inhibition, where regulated GABA flux has been linked to sensory coding, network excitability, and behavior across circuits. Its contribution to ischemic pathology is also assessed, with attention given to the timing-dependent shift from acute injury mechanisms to post-stroke recovery windows. Finally, emerging evidence for BEST1 in microglia and neurons is weighed cautiously and framed as a tractable agenda for direct testing. A more rigorous BEST1 field is argued to depend on cell-type-resolved genetics, validated localization pipelines, and temporally precise intervention studies.