{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMYO9B encodes an unconventional myosin that plays an essential role in the regulation of the intestinal epithelial barrier. Several genetic studies have robustly associated variants in MYO9B with disorders characterized by impaired barrier function—including celiac disease, inflammatory bowel disease, and other autoimmune conditions—as well as complications such as refractory celiac disease and type 1 diabetes. These observations support that altered MYO9B expression or function may compromise epithelial cytoskeletal organization and tight junction integrity, influencing intestinal permeability and subsequent immune activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, MYO9B is unique among myosins because it couples a motor domain that traverses actin filaments with an intrinsic Rho GTPase–activating (RhoGAP) domain that modulates RhoA activity. Biochemical and structural studies have demonstrated that MYO9B functions as a single‐headed processive motor with a rate‐limiting ATP hydrolysis step, and its RhoGAP activity is fine‐tuned by binding partners that compete with RhoA. This dual functionality enables MYO9B to locally regulate actin cytoskeletal dynamics during processes such as cell migration and epithelial wound healing, where spatial control of RhoA activity is critical."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging studies have broadened the spectrum of MYO9B functions beyond the intestinal epithelium. Notably, a circular RNA derived from MYO9B has been implicated in promoting breast cancer cell proliferation, migration, and invasion via microRNA sponging, while alterations in MYO9B function are also associated with aberrant immune responses observed in malignant pleural effusion. Furthermore, genetic association studies have linked MYO9B variants with susceptibility to neuropsychiatric disorders such as schizophrenia, reinforcing its role in modulating cell migration and immune cell differentiation in diverse tissues. These findings argue for a multifaceted role of MYO9B in coordinating actin dynamics, cell polarity, and signaling pathways that are critical for both normal cellular functions and the pathogenesis of a broad array of diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alienke J Monsuur, Paul I W de Bakker, Behrooz Z Alizadeh, et al. 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