{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTUBB6, a member of the β‐tubulin multigene family (class V), is expressed ubiquitously in several normal tissues and shows a distinctive alteration in tumors. In normal cells, its balanced expression contributes to the intricate tubulin isotype repertoire, whereas in diverse cancers—including colorectal and bladder carcinomas—TUBB6 levels are frequently downregulated or deregulated, implicating it as a potential diagnostic and predictive biomarker for malignancy and treatment response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in defining cellular identity, TUBB6 is a key regulator of microtubule dynamics. It contributes to the maintenance of a dynamic microtubule network by interacting with microtubule‐associated proteins. For instance, TUBB6 directly associates with LRRK2 via its Roc domain, an interaction that is sensitive to pathogenic mutations, thereby influencing microtubule stability in neuronal processes. Moreover, increased TUBB6 expression disrupts the microtubule network, impairing the execution of pyroptosis, a form of proinflammatory cell death, by rendering microtubules less stable."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic alterations in TUBB6 further underscore its importance in neurodevelopment. A heterozygous missense mutation in TUBB6 has been linked to congenital cranial dysinnervation disorders, manifesting as non‐progressive facial palsy and related cranial nerve dysfunctions. This evidence positions TUBB6 among critical tubulin isoforms whose mutations contribute to neurodevelopmental syndromes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of specialized cell functions, differential regulation of TUBB6 is essential for cytoskeletal reorganization. For example, osteoclasts express markedly elevated levels of TUBB6, which is necessary for the proper formation of podosomes and the sealing zone that underlies efficient bone resorption. Modulation of TUBB6 expression in these cells directly affects their resorptive activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLastly, broader epigenomic analyses in inflammatory conditions such as ulcerative colitis dysplasia have evaluated tubulin isotypes among a spectrum of candidate biomarkers. Although the direct mechanistic role of TUBB6 in this context remains to be fully elucidated, its inclusion in such studies highlights the emerging interest in tubulin isoforms as modulators of diverse disease phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Luis J Leandro-García, Susanna Leskelä, Iñigo Landa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A cellular genome-wide association study reveals human variation in microtubule stability and a role in inflammatory cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E13-06-0294"}], "href": "https://doi.org/10.1091/mbc.E13-06-0294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24173717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24173717"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bernard M H Law, Victoria A Spain, Veronica H L Leinster, et al. 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