{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:20:29Z","timestamp":1792113629306,"version":"4.4.0"},"reference-count":330,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIDCR","award":["UG3\/UH3DE028850"],"award-info":[{"award-number":["UG3\/UH3DE028850"]}]},{"name":"NIH\/NIDCR","award":["R01DE029445"],"award-info":[{"award-number":["R01DE029445"]}]},{"name":"NIH\/NIDCR","award":["R01DE034447"],"award-info":[{"award-number":["R01DE034447"]}]},{"name":"NIH\/NIDCR","award":["R90DE022528"],"award-info":[{"award-number":["R90DE022528"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Dental enamel, the final product of amelogenesis, is a highly mineralized bioceramic that becomes acellular and non-regenerating after tooth eruption. This paper reviews literature that explores inorganic phosphate (Pi) transport during the process of enamel formation or amelogenesis. Evidence from transcriptomics, immunolocalization, and physiology implicates ameloblast-specific sodium-dependent Pi uptake by type III sodium\u2013phosphate cotransporters SLC20A1 (PiT1) and SLC20A2 (PiT2), and by type IIb sodium\u2013phosphate cotransporter SLC34A2 (NaPi-IIb) with stage-specific basal (proximal) or apical (distal) enrichment, and pH-dependent expression. Controlled Pi efflux to the enamel space has been partly attributed to xenotropic and polytropic retrovirus receptor (XPR1) mediated Pi export during maturation-stage amelogenesis. These amelogenesis-specific Pi fluxes operate within a polarized cellular framework in which Ca2+ delivery and extrusion, together with bicarbonate-based buffering regulated by cystic fibrosis transmembrane conductance regulator (CFTR), Solute carrier family 26 (SLC26) exchangers, anion exchanger 2 (AE2), and electrogenic sodium bicarbonate cotransporter 1 (NBCe1), at-least partially contribute to cellular Pi activity, and neutralize protons generated as the extracellular hydroxyapatite-based enamel matures. Disruption of phosphate handling reduces crystal growth and final mineral content of enamel, and produces hypomineralized or hypomature enamel with opacities, post-eruptive breakdown, and greater caries susceptibility. This review integrates multi-modal findings to appraise established features of ameloblast Pi handling, define constraints imposed by pH control and Ca2+ transport, and identify gaps in ion transporter topology and trafficking dynamics.<\/jats:p>","DOI":"10.3390\/cells14221821","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T09:44:53Z","timestamp":1763631893000},"page":"1821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Enamel Maturation as a Systems Physiology: Ion Transport and Pi Flux"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4347-4316","authenticated-orcid":false,"given":"Mehrnaz","family":"Zarinfar","sequence":"first","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Department of Biomedical Sciences, Herman Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marziyeh","family":"Aghazadeh","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Department of Biomedical Sciences, Herman Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8418-9060","authenticated-orcid":false,"given":"Rucha Arun","family":"Bapat","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Department of Biomedical Sciences, Herman Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbin","family":"Ji","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Department of Biomedical Sciences, Herman Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Paine","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Department of Biomedical Sciences, Herman Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1152\/physrev.00030.2016","article-title":"Dental Enamel Formation and Implications for Oral Health and Disease","volume":"97","author":"Lacruz","year":"2017","journal-title":"Physiol. 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