Altogether, these results illustrate a role of CLN3 in regulating POS phagocytosis in human RPE cells and (i) suggest a role of primary RPE dysfunction in CLN3-associated retinal degeneration and (ii) indicate gene-therapy targeting RPE cells as a potential treatment option to suppress photoreceptor cell loss in CLN3 disease caused due to the common 966 bp deletion. The gene discussed is CLN3; the disease is retinal degeneration.