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Consistent with human phenotypes, <jats:italic>Odaph<\/jats:italic>-null mice exhibit defective enamel mineralization with ameloblast detachment from the enamel surface. To elucidate the mechanistic basis, we investigated ODAPH\u2019s role in ameloblast adhesion and mineralization using ameloblast-lineage cells (ALCs). Key findings demonstrate that <jats:italic>Odaph<\/jats:italic> overexpression enhanced Laminin\u03b32 (LAMC2)\/Integrin\u03b26(ITGB6)\/TGF-\u03b21\/Alkaline Phosphatase(ALP) pathway activity. Notably, co-immunoprecipitation confirmed interactions between ODAPH and LAMC2. Functional analyses revealed that ITGB6 activates the TGF-\u03b21\/ALP signaling cascade. Inhibition of integrin (CWHM-12) abrogates ODAPH-mediated TGF-\u03b21\/ALP induction. TGF-\u03b21 positively regulates both LAMC2\/ITGB6 expression and ALP activity. These results establish that ODAPH orchestrates ameloblast adhesion and mineralization via the LAMC2\/ITGB6\/TGF-\u03b21\/ALP signaling axis.<\/jats:p>","DOI":"10.1371\/journal.pone.0328263","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T17:33:14Z","timestamp":1752859994000},"page":"e0328263","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Odontogenesis-associated phosphoprotein (ODAPH) Promotes Ameloblast adhesion and alkaline phosphatase (ALP) expression via LAMC2\/ ITGB6\/TGF-\u03b21 signaling 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