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We found that\n                    <jats:italic>Epfn<\/jats:italic>\n                    was expressed in parathyroid glands, and\n                    <jats:italic>Epfn\u2010<\/jats:italic>\n                    knockout mice displayed elevated serum parathyroid hormone (PTH) concentrations, decreased bone volume, and intracranial ectopic calcification. To investigate the role of Epfn in the regulation of\n                    <jats:italic>PTH<\/jats:italic>\n                    expression, parathyroid gland explant and parathyroid cell line culture methods were used.\n                    <jats:italic>Epfn<\/jats:italic>\n                    expression was found to be upregulated in response to an increase in extracellular calcium concentration, whereas\n                    <jats:italic>PTH<\/jats:italic>\n                    expression was downregulated, thus demonstrating an inverse correlation. Forced expression of\n                    <jats:italic>Epfn<\/jats:italic>\n                    inhibited\n                    <jats:italic>PTH<\/jats:italic>\n                    gene expression and\n                    <jats:italic>PTH<\/jats:italic>\n                    promoter reporter activity in parathyroid cells. In addition, with a high extracellular calcium concentration,\n                    <jats:italic>Epfn<\/jats:italic>\n                    silencing in cultured parathyroid glands failed to block\n                    <jats:italic>PTH<\/jats:italic>\n                    gene expression. ChIP\u2010qPCR analysis also revealed Epfn binding in the proximal region of the\n                    <jats:italic>PTH<\/jats:italic>\n                    promoter, which was accelerated in the presence of a high concentration of calcium ions. The results from our\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    analyses suggest that Epfn is a newly identified negative regulator of\n                    <jats:italic>PTH<\/jats:italic>\n                    transcription by regulating the proximal\n                    <jats:italic>PTH<\/jats:italic>\n                    promoter. Furthermore, the expression of\n                    <jats:italic>Epfn<\/jats:italic>\n                    was significantly reduced in parathyroid adenomas of primary hyperparathyroidism patients. The identification of Epfn as a potential therapeutic target for the control of PTH production in hyperparathyroidism patients opens new avenues for targeted treatment approaches.\n                  <\/jats:p>","DOI":"10.1111\/febs.70085","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T20:41:53Z","timestamp":1743540113000},"page":"3659-3675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular mechanism for transcriptional regulation of the parathyroid hormone gene by Epiprofin"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9904-1037","authenticated-orcid":false,"given":"Takashi","family":"Nakamura","sequence":"first","affiliation":[{"name":"Division of Molecular Pharmacology &amp; Cell Biophysics, Department of Disease Management Dentistry Tohoku University Graduate School of Dentistry  Sendai 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