{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ANKS4B is a multifunctional adaptor protein that plays a critical role in organizing specialized apical structures in epithelial cells. In transporting epithelia, particularly in the brush border of intestinal enterocytes and in stereocilia, ANKS4B localizes to the distal tips of microvilli where it functions as an essential scaffold within the intermicrovillar adhesion complex (IMAC). Through direct interactions with USH1C (also known as harmonin) and the actin-associated motor MYO7B, ANKS4B helps form a tripartite complex that links protocadherin‐based adhesion molecules to the actin cytoskeleton, thereby driving intermicrovillar adhesion and ensuring proper brush border assembly and maintenance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Detailed biochemical and structural studies have revealed that ANKS4B contains a novel, noncanonical apical targeting sequence—featuring coiled‐coil and membrane-binding motifs—that is required for its precise localization to the brush border and for mediating the assembly of the IMAC. Moreover, ANKS4B’s participation in forming dynamic, phase‐separated condensates with USH1C and MYO7B suggests that multivalent interactions underpin the stabilization of tip‐link complexes that are necessary for the structural integrity and force sensing of these actin-based protrusions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its structural role in epithelial morphogenesis, ANKS4B has been identified as a direct transcriptional target of HNF4α in pancreatic β-cells, where it modulates the endoplasmic reticulum stress response by interacting with GRP78. Overexpression of ANKS4B in this context increases susceptibility to ER stress-induced apoptosis, thereby implicating ANKS4B in the regulation of β-cell function in diabetes mellitus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, dysregulated expression of ANKS4B has emerged from studies in various cancer types—including gastric, colon, and ovarian cancers—as a hub gene associated with disease progression and prognosis. These studies suggest that ANKS4B may serve as a valuable biomarker for clinical stratification and might influence tumor behavior through mechanisms that remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, preliminary findings have implicated ANKS4B in the cellular response to viral infection, as evidenced by studies investigating its relationship with Zika virus, although further research is required to clarify its precise role in this context."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Scott W Crawley, Meredith L Weck, Nathan E Grega-Larson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ANKS4B Is Essential for Intermicrovillar Adhesion Complex Formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2015.12.022"}], "href": "https://doi.org/10.1016/j.devcel.2015.12.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26812018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26812018"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "I-Mei Yu, Vicente J Planelles-Herrero, Yannick Sourigues, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mechanistic Basis of Organization of the Harmonin/USH1C-Mediated Brush Border Microvilli Tip-Link Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2015.12.020"}], "href": "https://doi.org/10.1016/j.devcel.2015.12.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26812017"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26812017"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yunyun He, Jianchao Li, Mingjie Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.09.027"}], "href": "https://doi.org/10.1016/j.celrep.2019.09.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31644917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31644917"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maura J Graves, Samaneh Matoo, Myoung Soo Choi, et al. 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