AMBN (ameloblastin) is a secreted extracellular matrix protein essential for dental enamel mineralization and structural organization 1. As an intrinsically disordered protein, AMBN functions through multiple mechanisms: it facilitates cross-linking with amelogenin during enamel matrix formation 2, forms oligomers via an exon 5-encoded sequence 3, and binds calcium ions, suggesting roles in both biomineralization and calcium homeostasis 3. AMBN acts as a matricellular protein mediating cell-matrix adhesion, cell signaling, and stabilization of prismatic enamel morphology through amphipathic helix and multitargeting domains 1. AMBN is processed by proteases MMP-20 and KLK-4 during enamel development, with its two alternatively spliced isoforms exhibiting distinct proteolytic profiles that may influence calcium buffering and signaling cascades 2. The human AMBN gene contains 13 protein-coding exons producing isoforms differing by ~15 amino acids 3. Biallelic AMBN mutations cause autosomal recessive amelogenesis imperfecta with hypoplastic enamel phenotypes 4. AMBN is enamel-specific; knockout mice show failed enamel ribbon initiation and pathological mineralization without affecting dentin or nondental tissues 4. AMBN variants are among genes with largest impact on genetic caries susceptibility 5. Digenic inheritance with ENAM mutations increases enamel severity 6.