Alkaline phosphatase (AP, EC 126.96.36.199.) is a metalloenzyme that belongs to a family of
ectonucleotidases. The other members of ectonucleotidase family are ecto-nucleoside triphosphate
diphosphohydrolases (E-NTPDases), ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPPs) and
ecto-5ʹ-nucleotidase (e5ʹNT). These ectonucleotidases are responsible for hydrolyzing extracellular
nucleotides to nucleosides including adenosine. Many of these extracellular nucleotides and adenosine are important
signaling molecules that act on their respective receptors (adenosine activated P1 receptor; nucleotide activated P2
receptor, each having many sub-types) and are therefore responsible for triggering cellular responses that lead to
important physiological and immunological changes. A dedicated, concerted cohort of ectonucleotidases is responsible for
controlling the availability of these extracellular signaling molecules at their respective receptors. Inhibitors of these
ectonucleotidases provide the means by which these cellular processes can be modulated. This mini review has been
written in the wake of mounting evidence of potential therapeutic benefits associated with inhibition of alkaline
phosphatases and aims to provide prolific leads to design more potent and selective AP inhibitors.
Keywords: Alkaline phosphatase, ectonucleotidase, inhibitors of alkaline phosphatase, mineralization defects, tissue nonspecific
alkaline phosphatase (TNAP), tissue specific alkaline phosphatase.
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