{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe recent studies collectively reveal that TTLL5 is a polyglutamylase with critical functions in specialized cellular structures. In the retina, TTLL5 mediates the addition of glutamate side‐chains to RPGR(ORF15), a process essential for proper protein trafficking within the photoreceptor’s connecting cilium. Disruption of this posttranslational modification leads to mislocalization of cone opsins and progressive photoreceptor degeneration, thereby providing a mechanistic link between defective glutamylation and retinal dystrophy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, TTLL5 plays a key role in the male reproductive system. Elevated expression of TTLL5 in the testis supports its involvement in sperm development, where it is essential for proper polyglutamylation of α‐tubulin within axonemal structures. Mutations in TTLL5 result in aberrant axoneme architecture and compromised sperm motility, thereby leading to male infertility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, these findings exemplify a broader paradigm in which tissue‐selective, posttranslational modification pathways are crucial for the maintenance of highly specialized cellular functions. Although one of the provided studies focused on the coordinated regulation of keratin‐associated proteins in hair—a process governed by factors like HOXC13"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "—none of the abstracts directly addressed the function of LINC00552. Thus, while TTLL5’s dual roles in photoreceptor integrity and sperm motility are now emerging as central to retinal health and male fertility, any potential contribution of LINC00552 to these processes remains to be elucidated.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xun Sun, James H Park, Jessica Gumerson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1523201113"}], "href": "https://doi.org/10.1073/pnas.1523201113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27162334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27162334"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nicola Bedoni, Lonneke Haer-Wigman, Veronika Vaclavik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw282"}], "href": "https://doi.org/10.1093/hmg/ddw282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28173158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28173158"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Geun-Shik Lee, Yuanzheng He, Edward J Dougherty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.453936"}], "href": "https://doi.org/10.1074/jbc.M113.453936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23558686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23558686"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nathanael D Pruett, Tatiana V Tkatchenko, Luis Jave-Suarez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Krtap16, characterization of a new hair keratin-associated protein (KAP) gene complex on mouse chromosome 16 and evidence for regulation by Hoxc13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M404331200"}], "href": "https://doi.org/10.1074/jbc.M404331200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15385554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15385554"}]}]}]}