Age-related macular degeneration (AMD) is the most common cause of irreversible blindness. We do not know the cause of the disease and have inadequate prevention and treatment strategies for those at risk or affected. The greatest risk factors include age and race, with the white population at the highest risk for the disease. We developed the hypothesis that pigmentation in the retinal pigment epithelium (RPE) protects darkly pigmented individuals from AMD. We have tested this hypothesis in multiple ways including dissecting the pigmentation pathway in RPE using albinism-related tools, identification of a G protein-coupled receptor in the pigmentation pathway that drives expression of trophic factors, and using a very large retrospective chart analysis to test whether the ligand for the receptor prevents AMD. In total, our results indicate that pigmentation of the RPE is a cornerstone of RPE-retinal interaction and support and that the receptor in the pigmentation pathway most likely underlies the racial bias of the disease. The ligand for that receptor is an ideal candidate as a preventative and treatment for AMD. Here we summarize these results, discussing the research in its entirety with one overall goal, treatment or prevention of AMD.