Proteomic Alterations in Hypomineralised Enamel: A Systematic Review

Background: Developmental enamel hypomineralisation is characterised by qualitative defects in enamel mineralisation that affect both primary and permanent dentitions. Proteomic studies have provided novel insights into the molecular mechanisms underlying these conditions; however, an updated critical appraisal integrating the available evidence across both Molar-Incisor Hypomineralisation (MIH) and Hypomineralised Second Primary Molars (HSPM) is needed. Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception until 30 July 2026. Observational and laboratory studies examining proteomic changes in enamel, saliva, or other oral biological samples from individuals diagnosed with MIH or HSPM were included. Risk of bias was assessed using the revised Joanna Briggs Institute (JBI) tool and the Quality Assessment Tool for In Vitro Studies (QUIN). Results: Ten reports satisfied the inclusion criteria, representing nine independent primary datasets. Consistent findings included increased retention of serum-derived proteins, particularly albumin, alongside enrichment of protease inhibitors and inflammatory proteins within hypomineralised enamel. Additionally, alterations in proteins involved in enamel matrix processing and maturation, including matrix metalloproteinase-20 (MMP20) and kallikrein-related peptidase 4 (KLK4), were identified. Salivary analyses revealed quantitative differences in proteins involved in immune, inflammatory and mineralisation-related pathways. Both shared and distinct proteomic features were observed across hypomineralised enamel in the primary and permanent dentitions. Conclusions: Current evidence indicates recurrent proteomic alterations in developmental enamel hypomineralisation, particularly impaired enamel maturation, abnormal retention of serum-derived proteins, and alterations in inflammatory pathways. Further standardised proteomic studies are needed to validate these findings and assess their potential as biomarkers.