{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPTPRQ encodes a receptor‐type protein tyrosine phosphatase that is critical for the development and maintenance of auditory function. Multiple alternatively spliced isoforms produce proteins with a variable number of fibronectin type III (FN3) repeats, a transmembrane domain, and a catalytic phosphatase domain. These structural features are required for the maturation of cochlear hair bundles—specifically the organization of stereocilia—and any disruption, through missense, nonsense, or frameshift mutations, is commonly associated with sensorineural hearing loss (SNHL) and vestibular dysfunction. Both recessive and, less frequently, dominant mutations have been reported, with the severity, onset, and progression of hearing impairment varying considerably among affected individuals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n \nIn addition to its essential role in auditory physiology, PTPRQ functions as a phosphatidylinositol phosphatase. This activity is paramount in modulating intracellular phosphoinositide levels, which in turn affects downstream Akt/PKB signaling pathways that govern cell survival, proliferation, and differentiation. For instance, studies in mesenchymal stem cells indicate that downregulation of PTPRQ during early adipogenesis correlates with reduced adipocyte differentiation via decreased phosphatidylinositol phosphate levels. Structural analyses further reveal a uniquely flat active-site pocket accommodating bulky phosphoinositide substrates, a feature that may also influence the enzyme’s involvement in carcinogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": "\n \nBeyond its roles in hearing and cellular signaling, PTPRQ has emerged as a potential biomarker in non‐auditory disorders. Proteomic analyses have identified PTPRQ in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus, where its concentration may help differentiate these patients from those with Alzheimer’s disease, as well as potentially predict shunt responsiveness. Collectively, these findings underscore the functional versatility of PTPRQ and its importance in both sensory and broader cellular contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Margit Schraders, Jaap Oostrik, Patrick L M Huygen, et al. 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