The retinal pigment epithelium (RPE) consists of a monolayer of post-mitotic cells that function as professional phagocytes. Each day, each RPE cell ingests and degrades the distal region of ~200 photoreceptor outer segments (POSs). This large daily degradative task of the RPE, throughout the life of an organism, often exacts a toll on retinal health. Inefficiencies in POS phagosome degradation are primary contributors to the progression of macular degenerations. Age-related macular degeneration is the leading cause of blindness among the elderly. Our studies have demonstrated the importance of phagosome motility in efficient phagosome maturation and degradation, with defects leading to RPE pathogenesis. We have found that the newly-formed phagosomes associate with the unconventional myosin, myosin-7a, which appears to deliver to the phagosomes through the actin-rich apical domain to the cell body. In the cell body, live-cell imaging studies show that the phagosomes associate with kinesin-1 and cytoplasmic dynein, and undergo bidirectional movements along microtubules, with an overall bias towards the basal region of the cell, where the plus ends of vertical microtubules are located. Along the way, they interact transiently with endolysosomes. In a model of Stargardt macular degeneration, a monogenic dominant disorder, mutant protein is expressed by the photoreceptor cells and localizes in the POSs. Resulting POS phagosomes have aberrant association with RAB7A and microtubule motor proteins, and are degraded more slowly. This cell non-autonomous effect leads to RPE pathogenesis, which, in turn, leads to a second cell non-autonomous step in which the photoreceptors die due RPE pathology. Our results show how the content of a phagosome can affect the association of motor proteins, and thus the motility of phagosomes, leading to altered rates of maturation and degradation.