{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ciliogenesis‐associated kinase 1 (CILK1), also known as intestinal cell kinase (ICK), is a highly conserved serine/threonine kinase that plays a critical role in modulating the structure and function of primary cilia. Localized predominantly at the proximal region of cilia near the basal bodies, CILK1 regulates ciliary length and intraflagellar transport by phosphorylating key substrates, thereby ensuring proper assembly and disassembly of the ciliary compartment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Disruption of CILK1 function, as observed in knockout models, leads to elongated cilia and aberrant Sonic Hedgehog signaling, which underlies several congenital disorders such as endocrine-cerebro-osteodysplasia (ECO) syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Precise activation of CILK1 requires its nuclear localization and dual phosphorylation of its conserved TDY motif—a process that is critically dependent on upstream kinases like CAK1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Mutations such as the R272Q variant impair nuclear translocation and kinase activity of CILK1, thereby disrupting ciliary homeostasis and downstream developmental signaling cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings underscore the pivotal role of CILK1 in maintaining ciliary integrity and highlight how its dysregulation contributes to developmental pathology and may influence disease processes where altered ciliary dynamics are implicated."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ying Yang, Niina Roine, Tomi P Mäkelä "}, {"type": "b", "children": [{"type": "t", "text": "CCRK depletion inhibits glioblastoma cell proliferation in a cilium-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/embor.2013.80"}], "href": "https://doi.org/10.1038/embor.2013.80"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23743448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23743448"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Heejung Moon, Jieun Song, Jeong-Oh Shin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1323161111"}], "href": "https://doi.org/10.1073/pnas.1323161111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24853502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24853502"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zheng Fu, Melanie J Schroeder, Jeffrey Shabanowitz, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Identification of yin-yang regulators and a phosphorylation consensus for male germ cell-associated kinase (MAK)-related kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00816-06"}], "href": "https://doi.org/10.1128/MCB.00816-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16954377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16954377"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Piya Lahiry, Jian Wang, John F Robinson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A multiplex human syndrome implicates a key role for intestinal cell kinase in development of central nervous, skeletal, and endocrine systems."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.12.017"}], "href": "https://doi.org/10.1016/j.ajhg.2008.12.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19185282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19185282"}]}]}]}