While the degradation of PPi to Pi by the tissue non-specific alkaline phosphatase (TNAP) maintains bone mineralization [1, 14, 15], reduced PPi levels, as a consequence of biallelic loss-of-function mutations in ENPP1, can result in neonatal vascular calcification (Generalized Arterial Calcification of Infancy type 1, GACI type 1) [16] and a rare form of FGF23-dependent rickets (Autosomal Recessive Hypophosphatemic Rickets type 2, ARHR2). This evidence concerns the gene ENPP1 and hypophosphatemic rickets, autosomal recessive, 2.