Studies in PHOSPHO1‐deficient mice (Phospho1−/−) display elevated PPi levels and decreased plasma TNAP activity(9, 10, 11) and present skeletal abnormalities, including fractures, bowed long bones, osteomalacia, and scoliosis in the early stage of life that resemble HPP, and thus are here referred to as a model of pseudo‐HPP.(11, 12, 13) The pathophysiology of rickets/osteomalacia and dental disease in HPP and Phospho1−/− mice can be explained by the accumulation in the extracellular matrix of PPi, a potent mineralization inhibitor(14) and one of the natural substrates of TNAP.(15, 16, 17). The gene discussed is ALPL; the disease is osteomalacia.