{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KANK1 is emerging as a multifunctional scaffold protein that plays several crucial roles in regulating cytoskeletal dynamics, cell adhesion, and signal transduction. In the cytoplasm, KANK1 bridges the gap between dynamic microtubules and integrin‐mediated adhesion sites by directly interacting with proteins such as kinesin family member 21A (KIF21A) and talin. These interactions help orchestrate the formation and stabilization of cortical microtubule networks at focal adhesions, thereby influencing cell polarity and migration."}, {"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 In addition, KANK1 is important for regulating Rho GTPase signaling in specialized cells such as podocytes, with loss-of-function mutations impairing slit diaphragm integrity and contributing to steroid-resistant nephrotic syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n KANK1 has also been implicated as a tumor suppressor. In several malignancies—including renal cell carcinoma, gastric cancer, oral squamous cell carcinoma, and lung cancer—downregulation or loss of KANK1 (often via promoter methylation or deletion) correlates with enhanced cell proliferation, migration, and invasion, whereas restoration of its expression promotes apoptosis and cell-cycle arrest."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its cytoplasmic roles, KANK1 can shuttle to the nucleus where it has been linked to the regulation of β‐catenin–dependent transcription, suggesting that it may also influence gene expression programs that underpin cell proliferation and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural studies have begun to reveal how the ankyrin repeat domain of KANK1 mediates highly specific binding to partners like KIF21A—a process that is vulnerable to disruption by disease‐associated mutations—and further bolster its role as a key integrator of cytoskeletal and adhesion-related signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, genome-wide association studies have implicated genetic variants near KANK1 in metabolic regulation and in susceptibility to nicotine dependence, underscoring its broader impact on human physiology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KANK1 functions as a critical adaptor that links the dynamic microtubule and actin cytoskeletons to sites of cell adhesion, modulates intracellular signaling pathways that control cell migration and survival, and acts as a tumor suppressor in various tissues.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Babet van der Vaart, Wilhelmina E van Riel, Harinath Doodhi, et al. 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