Aside from its well-accepted promotion of ATP efflux, PPi and adenosine generation [11,13,243], ABCC6 also influences extracellular nucleotide metabolism in central and peripheral tissues [20] and cells ([15] and Figure 4), and its deficiency creates a disruptive environment not only conducive to ectopic calcification but likely to other pathogenic processes such as vascular abnormalities [56,97], inflammation [159,160,161], atherosclerosis and dyslipidemia [54]. The gene discussed is ABCC6; the disease is atherosclerosis.