Vitelliform macular dystrophy is an eye disorder that leads to the progressive loss of central vision. The early-onset form of the disease – known as Best vitelliform macular dystrophy (BMD) – is caused by mutations in BEST1. Bestrophin-1, the protein encoded by this gene, is highly expressed in the retinal pigment epithelium (RPE) and has been implicated with a function in anion transport, intracellular Ca2+ homeostasis and ion transport across organelle membranes. However, the molecular mechanisms underlying BMD pathology are still unclear. Olaf Strauss, Bernhard Weber and colleagues (p. 2988) now show that disease-associated missense mutations in bestrophin-1 affect its cellular localisation and alter cellular anion permeability. Using polarised MDCK II cells, the authors show that wild-type bestrophin-1 localises to the basolateral membrane. By contrast, nine of the 13 mutant proteins investigated are primarily found in the cytoplasm and four others show reduced membrane localisation. In addition, all mutants result in reduced anion permeability of the plasma membrane when compared with wild-type bestrophin-1. For these reasons, the authors propose that missense mutations in bestrophin-1 result in altered Cl− and H2O transport across the RPE epithelium and impair regulation of the cell volume. This disruption of RPE function – which is essential for photoreceptor viability – might, therefore, be involved in causing BMD.