{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:36:41Z","timestamp":1790858201543,"version":"4.1.0"},"reference-count":202,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["397519724"],"award-info":[{"award-number":["397519724"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hypophosphatasie Deutschland e.V.","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5\u2032-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme\u2019s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.<\/jats:p>","DOI":"10.3390\/biom10121648","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T20:27:15Z","timestamp":1607459235000},"page":"1648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Tissue-Nonspecific Alkaline Phosphatase\u2014A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-7169","authenticated-orcid":false,"given":"Daniel","family":"Liedtke","sequence":"first","affiliation":[{"name":"Institute for Human Genetics, Biocenter, Julius-Maximilians-University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Section of Pediatric Rheumatology and Osteology, University Children\u2019s Hospital of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Jakob","sequence":"additional","affiliation":[{"name":"Bernhard-Heine-Center for Locomotion Research, Julius-Maximilians-University W\u00fcrzburg, 97076 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Klopocki","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics, Biocenter, Julius-Maximilians-University W\u00fcrzburg, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Graser","sequence":"additional","affiliation":[{"name":"Bernhard-Heine-Center for Locomotion Research, Julius-Maximilians-University W\u00fcrzburg, 97076 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00223-015-0079-1","article-title":"Alkaline Phosphatase and Hypophosphatasia","volume":"98","author":"Whyte","year":"2016","journal-title":"Calcif. 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