Classic PXE is caused by EF mineralization in soft tissues due to biallelic ABCC6 (ATP-binding cassette, subfamily C, member 6; OMIM*603234) mutations and features yellowish skin papules and plaques in flexural areas (although in more severe cases an increase in skin laxity may occur), ophthalmological symptoms (asymptomatic peau d’orange and angioid streaks and in more advanced stages subretinal neovascularization, bleeding and scarring leading to legal blindness when untreated) and cardiovascular symptoms (peripheral artery disease, cardiac diastolic dysfunction) (Figure 3A) [34,35]. The gene discussed is ABCC6; the disease is peripheral arterial disease.