{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCochlin is a multifunctional extracellular matrix protein most notably expressed in sensory tissues. In the inner ear, it is highly expressed by fibrocytes within the spiral limbus, spiral ligament, and supporting structures, and its normal processing is critical for auditory and vestibular function. Mutations in COCH lead to the DFNA9 syndrome, a late‐onset, progressive sensorineural hearing loss and vestibular dysfunction characterized by acellular deposits and disrupted tissue architecture. In mouse models, both knock‐in and knock‐out strategies have revealed that mutant cochlin accumulation correlates with cochlear and vestibular pathology, while alterations in cochlin isoforms (including loss of the N‑terminal FCH/LCCL domain) are associated with neuroepithelial degeneration and stress responses in the inner ear."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the ocular compartment, cochlin has emerged as a key player in the regulation of intraocular pressure (IOP) and may thus contribute to primary open angle glaucoma. Proteomic analyses of glaucomatous trabecular meshwork have revealed abnormal cochlin deposits that co‐localize with extracellular matrix components, such as collagen, and mucopolysaccharides; under mechanical shear stress, cochlin multimerizes in a way that impairs its proteolytic degradation, thereby potentially disrupting aqueous humor outflow. Overexpression, reintroduction, or exogenous addition of cochlin leads to elevated IOP, whereas down‐regulation produces the converse effect, underscoring its role as a mechanosensor within the extracellular matrix of the eye."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in sensory organs, cochlin has been implicated in immune function and stem cell maintenance. In lymphoid tissues, follicular dendritic cells selectively express and liberate cleaved fragments of cochlin during inflammation, where its LCCL domain sequesters bacteria and orchestrates local cytokine production and immune cell recruitment in bacterial infections. Furthermore, in embryonic stem cells, cochlin—up‐regulated by BMP4 signaling via Smad pathways—supports self‑renewal and suppresses neural differentiation, thereby acting as an important downstream effector of BMP signaling. Interestingly, in a noise exposure model, the absence of cochlin offers protective effects against auditory threshold shifts, highlighting its multifaceted role in modulating both innate immunity and cellular responses to mechanical stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "N G Robertson, B L Resendes, J S Lin, et al. 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