ENPP1 and ankylosis: For HA synthesis, alkaline phosphatase (ALP) hydrolyses pyrophosphate (PPi) to inorganic phosphate, ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) synthesizes PPi, and ankylosis human (ANKH) transports PPi to the extracellular matrix where HA is formed [12].