SignificanceRetinitis pigmentosa (RP) is a blinding disease affecting 2 million people worldwide. The night vision of RP patients is affected first due to the expression of a disease gene in rod photoreceptors. This loss of rod-mediated night vision is followed by a bystander effect on cone photoreceptors, which results in loss of daylight vision. The mechanism of the secondary cone degeneration is unclear. We used genetically modified mice and electrophysiology to explore this question. We found that slowing down the recycling of vitamin A derivatives for the regeneration of opsin, a GPCR, could protect RP cone function and extend their survival. These studies reveal a unique pathway for RP cone degeneration and suggest potential therapies that could benefit RP patients.