The retina is a multi-layered structure lining the posterior segment of the eye. It consists of photoreceptors and retinal pigment epithelial cells (RPEpiC). Localization of RPEpiC is between the neurosensory retina and the choroid; forming the outer blood-retina barrier that controls the chemical composition of the subretinal space. RPEpiC have specific polarized protein distributions within the cell. In contrast to other epithelia which normally faces an apical lumen devoid of matrix; the RPEpiC apical plasma membrane is in direct contact with the extracellular matrix. RPEpiC play a critical role in regulating the adjacent photoreceptor membrane turnover, retinoid metabolism, and protecting the retina from light-induced damages by the intracellular melanin, which suggests that RPEpiC may contribute to the pathogenesis of various ocular diseases such as proliferative retinopathy and age-related macular degeneration. Human Retinal Pigment Epithelial Cells provide an invaluable tool for understanding physiological and pathophysiological relevance in retina function and disease.