PXE is most commonly caused by biallelic pathogenic variants in the ABCC6 gene (ATP-binding cassette sub-family C member 6; OMIM* 603234), though rare patients have been reported with bi-allelic ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1; OMIM* 173335) or CYP2U1 (Cytochrome P450, Family 2, subfamily U, polypeptide 1; OMIM* 610670) variants; digenic inheritance with ABCC6/GGCX pathogenic variants (gamma-glutamyl carboxylase; OMIM* 137167) has also been reported [7,13,14]. Here, ENPP1 is linked to pseudoxanthoma elasticum (inherited or acquired).