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However, only recent studies clarified the isotype, regional distribution and subcellular localization of the AP expressed in the cerebral cortex of diverse mammalian species including the human. In the primate brain the discovery that the bone AP isotype (TNAP) is expressed provided the opportunity of a deeper understanding of the role of this enzyme in neuronal functions based on the knowledge acquired by studying the role of the enzyme in hypophosphatasia, mostly in bone mineralization. TNAP exhibits widespread substrate specificity and, in the brain, it is potentially involved in the regulation of molecules which play fundamental roles in signal transmission and development. In light of these observations, the localization of TNAP in the human cerebral cortex is of high significance when considering that epilepsy is often diagnosed in hypophosphatasia. 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