TNALP is an ectoenzyme that is attached to the outer plasma membrane via a glycosylphosphatidylinositol (GPI) anchor.(5,6) Absence of TNALP activity results in extracellular accumulation of natural substrates such as inorganic pyrophosphate (PPi ),(7,8) pyridoxal 5'-phosphate (PLP),(9,10) and phosphoethanolamine (PEA).(11) Since high concentrations of PPi result in a strong inhibition of hydroxylapatite crystal growth, normal mineralization of the systemic bones and teeth is impaired in HPP patients.(8,12) Pyridoxine-responsive seizures are also observed in some severe cases. Here, ALPL is linked to hypophosphatasia.