BEST2 (bestrophin 2) is a calcium-activated anion channel that mediates movement of chloride, bicarbonate, and glutamate across cell membranes 1. The protein functions as a ligand-gated anion channel where calcium binding triggers aperture dilation to permit anion transport 1. In colonic goblet cells, BEST2 localizes to the basolateral membrane and mediates bicarbonate transport critical for maintaining colonic lumen hydration and pH 2. In non-pigmented epithelium, intracellular glutamate binding activates BEST2, promoting glutamate efflux and chloride influx in trans 3. BEST2 gating involves a C-terminal auto-inhibitory segment that must be released for channel opening, with this segment determining functional specificity among bestrophin family members 1. Clinically, reduced BEST2 expression in colorectal cancer associates with poor prognosis and shorter overall survival 4. Enhanced BEST2 expression in keratinocytes suppresses psoriatic inflammation by inhibiting JAK2/STAT3 signaling 5. Small molecule activators, including 4-aminobenzoic acid (PABA), can rescue functional deficiency of BEST2 mutations, suggesting therapeutic potential for bestrophin-associated diseases 3.