AMELX (amelogenin X-linked) encodes a major structural protein of the developing enamel matrix 1 that plays a critical role in biomineralization and enamel formation. During amelogenesis, AMELX regulates crystallite formation and the structural organization of enamel during the secretory and maturation stages 2. The protein functions in calcium ion binding and hydroxyapatite interactions, essential for proper enamel mineralization 3. Mutations in AMELX cause X-linked amelogenesis imperfecta (AI types IE, IIB, and IIC), characterized by hypoplastic (thin) and/or hypomaturation (soft) enamel defects 4. Genotype-phenotype correlations reveal that amorphic mutations (large deletions, 5' truncations) cause hypoplastic-hypomaturation enamel with "snow-capped" appearance due to complete loss of function, while neomorphic variants (signal peptide defects, 3' truncations) produce severe hypoplastic/aplastic enamel through toxic cellular effects, including endoplasmic reticulum stress and potential apoptosis 4. AI represents an inherited group of developmental conditions affecting enamel structure and appearance in all or nearly all teeth, with prevalence ranging from 1:700 to 1:14,000 5. AMELX polymorphisms may also influence dental caries susceptibility, though evidence for specific variants remains limited 6. Clinical management requires early intervention with preventive and restorative approaches throughout childhood into adulthood 5.