ANKH and hypophosphatasia: Monogenic forms have been associated with mutations in genes determining the increase of ePPi as loss-of-function mutations in ANKH gene [32, 90], encoding for Inorganic Pyrophosphate Transport Regulator, PC-1, encoding for a nucleotide pyrophosphate synthetase [32], TNAP, encoding for tissue-non-specific alkaline phosphatase found in matrix vesicles and also associated with hypophosphatasia [91, 92].