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Rp1l1, or Retinitis pigmentosa 1-like 1, is a component of the photoreceptor cilium. Although its exact function remains unknown, it is crucial for photoreceptor biology. The gene is associated with pathways related to photoreceptor development and maintenance, and its importance lies in preventing photoreceptor-related diseases [1,2]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially be valuable for further functional studies of Rp1l1 in vivo.

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 study of 1204 Japanese patients with retinitis pigmentosa, variants in Rp1l1 were among the six genes that caused the disease in a significant proportion of patients [3]. In a Chinese cohort of inherited eye diseases, Rp1l1 had a diagnostic yield of de novo mutations of 5.88% [4]. A case report described an Indian patient with a homozygous variant in Rp1l1, presenting with ill-defined foveal mottling, sub-foveal hyper-reflective deposits, and outer retinal layer disruption, diagnosed with Rp1L1 maculopathy [5]. Additionally, the RP1L1 rs3924612 polymorphism was associated with early age-related macular degeneration development in certain female and age groups [6]. In patients with macular and cone/cone-rod dystrophy, mutations in Rp1L1 were identified [7]. In RP1L1-associated occult macular dystrophy, there was predominantly a deterioration of L-and M-cone-driven function in the perifovea, while rod-driven functions were normal [8]. In Taiwanese families with inherited retinal degeneration, probands affected by Rp1L1 sought medical help earlier [9]. A Chinese family was identified with a maculopathy case caused by new recessive compound heterozygous variants of Rp1L1 [10].

In conclusion, Rp1l1 is essential for photoreceptor biology, and its malfunction is strongly associated with various photoreceptor-related diseases, such as retinitis pigmentosa, occult macular dystrophy, and maculopathy. Although no KO/CKO mouse model-specific findings were in the provided abstracts, the existing human-based genetic and clinical studies highlight the significance of Rp1l1 in maintaining normal photoreceptor function and the potential implications for understanding and treating these diseases.

References:

1. Noel, Nicole C L, MacDonald, Ian M. 2020. RP1L1 and inherited photoreceptor disease: A review. In Survey of ophthalmology, 65, 725-739. doi:10.1016/j.survophthal.2020.04.005. https://pubmed.ncbi.nlm.nih.gov/32360662/

2. Liu, Jiali, Hayden, Melvin R, Yang, Ying. 2024. Research progress of RP1L1 gene in disease. In Gene, 912, 148367. doi:10.1016/j.gene.2024.148367. https://pubmed.ncbi.nlm.nih.gov/38485037/

3. Koyanagi, Yoshito, Akiyama, Masato, Nishiguchi, Koji M, Kubo, Michiaki, Sonoda, Koh-Hei. 2019. Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients. In Journal of medical genetics, 56, 662-670. doi:10.1136/jmedgenet-2018-105691. https://pubmed.ncbi.nlm.nih.gov/31213501/

4. Li, Wei, He, Xiang-Dong, Yang, Zheng-Tao, Li, Jian-Kang, He, Wei. . De Novo Mutations Contributes Approximately 7% of Pathogenicity in Inherited Eye Diseases. In Investigative ophthalmology & visual science, 64, 5. doi:10.1167/iovs.64.2.5. https://pubmed.ncbi.nlm.nih.gov/36729443/

5. Manayath, George J, Rokdey, Mayur, Verghese, Shishir, Saravanan, V R, Narendran, Venkatapathy. 2021. An extended phenotype of RP1L1 maculopathy - case report. In Ophthalmic genetics, 43, 392-399. doi:10.1080/13816810.2021.2021426. https://pubmed.ncbi.nlm.nih.gov/34965838/

6. Daniute, Ginte, Vilkeviciute, Alvita, Gedvilaite, Greta, Kriauciuniene, Loresa, Liutkeviciene, Rasa. 2021. RP1L1 rs3924612 gene polymorphism and RP1L1 protein associations among patients with early age-related macular degeneration. In Ophthalmic genetics, 43, 164-171. doi:10.1080/13816810.2021.2010770. https://pubmed.ncbi.nlm.nih.gov/34865606/

7. Birtel, Johannes, Eisenberger, Tobias, Gliem, Martin, Bolz, Hanno J, Charbel Issa, Peter. 2018. Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy. In Scientific reports, 8, 4824. doi:10.1038/s41598-018-22096-0. https://pubmed.ncbi.nlm.nih.gov/29555955/

8. Huchzermeyer, Cord, Fars, Julien, Kremers, Jan, Stingl, Krunoslav, Stingl, Katarina. . Photoreceptor-Specific Temporal Contrast Sensitivities in RP1L1-Associated Occult Macular Dystrophy. In Investigative ophthalmology & visual science, 64, 33. doi:10.1167/iovs.64.7.33. https://pubmed.ncbi.nlm.nih.gov/37342031/

9. Chen, Ta-Ching, Huang, Ding-Siang, Lin, Chao-Wen, Hu, Fung-Rong, Chen, Pei-Lung. 2021. Genetic characteristics and epidemiology of inherited retinal degeneration in Taiwan. In NPJ genomic medicine, 6, 16. doi:10.1038/s41525-021-00180-1. https://pubmed.ncbi.nlm.nih.gov/33608557/

10. Cao, Wen-Chao, Chen, Qing-Shan, Gan, Run, Huang, Tao, Yan, Xiao-He. 2024. New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy. In International journal of ophthalmology, 17, 107-112. doi:10.18240/ijo.2024.01.14. https://pubmed.ncbi.nlm.nih.gov/38239955/