The membrane-frizzled related protein (MFRP) is a retinal pigment epithelium (RPE) and ciliary epithelium-expressed gene of unknown function. Interest in MFRP stems from clinical manifestations that range from acute-angle closure glaucoma to microphthalmia and Retinitis pigmentosa in patients with MFRP mutations. Furthermore, the genetic ablation of Mfrp in mice results in an early-onset retinal disease with visible degeneration around 1mo of age and primary rod photoreceptor loss. Yet, little is known regarding the exact role of MFRP in the RPE, its underlying contribution to pathology, and the impacted mechanisms at the early stages of MFRP-related disease. This review presents a current overview of MFRP studies and poses outstanding questions that are crucial for understanding the involvement of MFRP in early-onset retinal degeneration. Such insight could pave the way for deciphering the molecular mechanisms associated with MFRP that are impacted during early stages in the retina, offering the potential to translate this knowledge into determining similarities and differences in mechanisms involved in late-stage retinal diseases.