{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KATNAL2 is a highly conserved member of the katanin family that shares structural features with the canonical microtubule‐severing enzyme, including an N‐terminal LisH domain and a C‐terminal AAA catalytic domain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Functional studies in cultured cells, mice, and Xenopus embryos have demonstrated that KATNAL2 plays a critical role in regulating microtubule dynamics, which is essential for proper cytokinesis, cell cycle progression, and ciliogenesis. In mouse and Xenopus models, loss or reduction of KATNAL2 activity leads to inefficient cytokinesis, formation of abnormal mitotic spindles, accumulation of excess centrioles, altered microtubule acetylation, and defects in cilia formation – processes that are particularly important in brain development and neurogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of human disease, multiple lines of genetic evidence have implicated KATNAL2 as a risk factor for neurodevelopmental disorders, including autism spectrum disorder, with rare coding variants and loss‐of‐function changes showing low penetrance in affected individuals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, alterations in KATNAL2 expression and methylation have been observed in various cancers, such as cervical, ovarian, and thyroid carcinomas, suggesting that aberrant regulation of its function may contribute to tumorigenesis by disturbing normal microtubule and cell cycle dynamics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the reproductive system, genetic studies have uncovered that biallelic mutations in KATNAL2 are associated with oligo‐astheno‐teratozoospermia in humans and contribute to impaired sperm maturation, abnormal head morphology, and flagellar defects in both patients and animal models, which indicates a pivotal role in spermatogenesis and male fertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence from population‐based genetic studies links KATNAL2 polymorphisms to specific neurobehavioral traits such as divergent thinking and creativity, which further underscores its multifaceted role in human biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these studies establish KATNAL2 as a multitasking enzyme involved in microtubule regulation that impacts critical aspects of cell division, ciliogenesis, neurodevelopment, reproductive function, and possibly tumorigenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ewa Joachimiak, Ewa Waclawek, Michal Niziolek, et al. 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