Hypophosphatasia (HPP, OMIM 146300, 241500, 241510) is a rare metabolic skeletal disorder caused by loss-of-function mutation in the ALPL gene, which encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), leading to decreased activity of alkaline phosphatase (ALP) and accumulation of endogenous substrates, including inorganic pyrophosphate (PPi), pyridoxal 5′-phosphate (PLP), and phosphoethanolamine (PEA). Here, ALPL is linked to hypophosphatasia.