Vitelliform macular dystrophy (VMD2) or Best dissease is autosomal dominant disorder characterized by egg-yolk macular lesions, decrease light peak in the electro-oculogram and juvenile age of onset. VMD2 gene encodes bestrophin-1 which is expressed in retinal pigment epithelium (RPE) cells, function as Cl- channel and to have regulatory function on voltage dependent Ca2+ channels. We investigated the expression, subcellular localization and intracellular function of endogenous and heterologously expressed bestrophin. Protein analysis of endogenous bestrophin-1 from freshly isolated RPE cells of adult human donor eyes, or heterologously expressed were performed with protein extracts from different cell compartments. The subcellular distribution of endogenous bestrophin-1 in human RPE cells revealed cytoplasmic expression pattern. Detection of heterologously expressed bestrophin revealed a comparable pattern in cytoplasmic compartment using bestrophin-GFP fusion construct. Fluorescence signal in cells were seen perinuclear. Cytosolic localization of endogenous bestrophin-1 freshly isolated from human RPE cells, and also heterogously expressed was confirmed by western blot analysis and support data obtained from immunocytochemistry. Here, bestrophin-1 is expressed in a different subcellular fraction containing cell organelles. DFG STR480/9-1