{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The gamma‐aminobutyric acid A receptor π subunit (GABRP) – a component of the multi‐subunit chloride channel complex – is emerging as a multifunctional molecule with context‐dependent roles in both normal physiology and disease. In neuropsychiatric disorders, for example, genetic variants in GABRP have been linked to schizophrenia and bipolar disorder, suggesting that altered receptor function may contribute to cognitive deficits and other neurobehavioral disturbances."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, the role of GABRP appears to be complex and somewhat context specific. In triple‐negative and basal‐like breast cancers, several studies report that GABRP is highly expressed on the cell surface and functionally contributes to tumor aggressiveness by sustaining epidermal growth factor receptor (EGFR) signaling. This activity promotes cancer cell stemness, migration, and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In contrast, another study found that GABRP expression is markedly down‐regulated in invasive breast carcinomas relative to normal breast epithelium, suggesting that loss of its normal expression may correlate with disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In cervical cancer, GABRP has been identified as a direct target of microRNA‑320c; restoration of miR‑320c levels attenuates cancer cell migration by suppressing GABRP expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, in pancreatic cancer, structural studies have shown that GABRP may serve as an accessible cell surface receptor that facilitates virus–receptor interactions, highlighting its potential utility in oncolytic adenovirus targeting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In reproductive biology, GABRP is expressed in early placental tissues. In first‐trimester placentas, its abundant expression in syncytiotrophoblasts gradually declines with gestational age."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Functionally, overexpression of GABRP in extravillous trophoblast cells increases apoptosis and limits their invasion, which may be linked to the pathogenesis of preeclampsia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Consistent with these findings, during uterine decidualization the activation of GABRP‐mediated GABA signaling suppresses stromal cell proliferation and promotes cell cycle arrest, suggesting a role in regulating the delicate balance of uterine cell differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the airways, GABRP is highly expressed in Club (Clara) cells. Its signaling is important for Club cell proliferation and their differentiation into goblet cells. Blockade of GABA receptor function (via GABRP) in mouse models significantly reduces mucin gene expression and goblet cell hyperplasia, hinting at a role in the pathogenesis of mucus‐overproducing conditions such as bronchial asthma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, genetic polymorphisms in the GABRP gene have been associated with susceptibility to systemic lupus erythematosus, particularly among female patients, underscoring its potential contribution to immune regulation."}, {"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, the body of evidence indicates that GABRP functions as a modulatory subunit that influences cell proliferation, differentiation, migration, and apoptosis in a tissue‐specific manner. These diverse roles underpin its involvement in neuronal signaling, tumor biology, reproductive processes, airway epithelial dynamics, and immune regulation, and collectively position GABRP as a potential diagnostic marker and therapeutic target in multiple disease settings.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T L Petryshen, F A Middleton, A R Tahl, et al. 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