The retinal pigment epithelium (RPE) is a highly polarized cell type in the retina which is specialized to support the photoreceptors and choroid. To assess the adequacy of RPE polarity in culture or altered RPE polarity under disease conditions in vivo, the polarized secretion of particular proteins can be monitored. Currently accepted basolateral secretion markers for RPE include the pro-angiogenic factor, VEGF, and extracellular matrix remodeling protein, TIMP-3. However, VEGF secretion is low enough that it often requires ELISA for detection, and TIMP-3 secretion is only modestly polarized to the basolateral side. We sought out an improved marker of basolateral secretion that is both highly expressed and highly polarized. Through a combination of bioinformatics analysis and RPE cell culture experiments, we identify insulin growth factor binding protein 5 (IGFBP5) as a more robust and convenient RPE basolateral marker compared to TIMP-3 and VEGF.