ACP4 encodes acid phosphatase 4, a transmembrane protein belonging to the histidine acid phosphatase family that plays critical roles in dental enamel formation and neuronal signaling. During amelogenesis, ACP4 is most strongly expressed in secretory stage ameloblasts and localizes primarily at Tomes' processes, where it regulates appositional growth of dental enamel by processing and regulating enamel matrix proteins around the mineralization front apparatus 1. The protein exhibits acid phosphatase activity and may dephosphorylate receptor tyrosine kinases, potentially modulating neuronal signaling pathways 2. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J), characterized by thin enamel with numerous ectopic mineralized nodules 1. Studies of ACP4-deficient mouse models demonstrate that loss of function leads to pathological ameloblast changes mid-way through the secretory stage, resulting in sporadic enamel ribbons that fail to elongate and aberrant needle-like crystal formation 1. Multiple disease-causing mutations have been identified in human families, including frameshift and missense variants that reduce protein expression, decrease homodimer formation ability, and diminish acid phosphatase activity 23. These findings establish ACP4 as essential for proper enamel mineralization and tooth development.