{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFXYD6 encodes the protein phosphohippolin, which primarily functions as a regulator of the Na⁺,K⁺-ATPase, modulating its kinetic properties to meet the specific physiological demands of neural tissues. In several studies, phosphohippolin’s brain‐enriched expression has been implicated in the maintenance of cation homeostasis and has been linked—with variable genetic association results—to susceptibility for schizophrenia. Some studies found significant associations between FXYD6 variants or haplotypes and schizophrenia, suggesting that aberrant expression or function of phosphohippolin may contribute toward the etiology of the disorder, whereas others did not detect such associations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies have demonstrated that FXYD6 plays a direct role in modulating the fundamental kinetics of the Na⁺,K⁺-ATPase. Specifically, experimental work in heterologous expression systems has shown that FXYD6 distinctively accelerates sodium deocclusion and enhances overall pump turnover rates. Moreover, it influences the pump’s intracellular ion selectivity and can affect its membrane surface expression, indicating that FXYD6 is crucial not only for enzymatic modulation but also for the proper trafficking of the pump."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐established role in neuronal ion regulation, FXYD6 has been implicated in oncogenic contexts. In hepatocellular carcinoma, up‐regulation of FXYD6 correlates with increased Na⁺,K⁺-ATPase levels and the activation of downstream signaling pathways (such as Src-ERK), which in turn enhance cancer cell migration and proliferation. Furthermore, aberrant expression and methylation patterns of FXYD6 have been proposed as potential biomarkers for glioma, thereby suggesting that FXYD6 may have multifaceted roles in both normal and pathological cell regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNotably, one study focusing on microRNA‑137’s role in osteosarcoma did not directly address FXYD6 function but was included in the aggregate analysis of related literature."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Khalid Choudhury, Andrew McQuillin, Vinay Puri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genetic association study of chromosome 11q22-24 in two different samples implicates the FXYD6 gene, encoding phosphohippolin, in susceptibility to schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/513475"}], "href": "https://doi.org/10.1086/513475"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17357072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17357072"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yoshihito Ito, Yukako Nakamura, Nagahide Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2008.04.010"}], "href": "https://doi.org/10.1016/j.neulet.2008.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18455306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18455306"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nannan Zhong, Rui Zhang, Chuan Qiu, et al. 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