Rp1l1, short for Retinitis pigmentosa 1-like 1, is a component of the photoreceptor cilium. Although its exact function remains unknown, it is suggested to play a crucial role in photoreceptor biology [1,2]. As photoreceptor cilia are involved in the transport of proteins and signal transduction necessary for photoreceptor function, Rp1l1 likely participates in related pathways important for the health and proper functioning of photoreceptor cells [1,2].

Pathogenic variants in Rp1l1 lead to photoreceptor diseases, including occult macular dystrophy (a cone degeneration) and retinitis pigmentosa (a rod disease) [1,2]. In a Japanese study of 1204 patients with retinitis pigmentosa, RP1L1 variants were among those causing the disease in a significant proportion of patients [3]. In an Indian patient with a homozygous variant in the RP1L1 gene, ophthalmological findings showed ill-defined foveal mottling, sub-foveal hyper-reflective deposits, and outer retinal layer disruption, expanding the phenotype spectrum associated with RP1L1 maculopathy [5]. Additionally, in a Chinese study of inherited eye diseases, RP1L1 was among the top 10 genes with a diagnostic yield of de novo mutations greater than 3.5% in their subgroups [4]. In a study on early age-related macular degeneration, the RP1L1 rs3924612 polymorphism was associated with the early AMD development [6].

In conclusion, Rp1l1 is essential for photoreceptor biology. Studies on patients with Rp1l1-related pathogenic variants have revealed its association with various photoreceptor-related diseases such as occult macular dystrophy, retinitis pigmentosa, and age-related macular degeneration. Understanding Rp1l1 can potentially offer insights into the mechanisms of these diseases and may contribute to the development of targeted therapies.