*6.3. Targeting ABCC6*

ABCC6 deficiency causes a broad spectrum of manifestations beyond calcification that includes vascular malformation (rete mirabile, carotid hypoplasia) [164], dyslipidemia, and atherosclerosis [93,94], as well as ischemic stroke [165], inflammation [159], premature cellular senescence in hepatic cells and dermal fibroblasts [166,167], increased infarct size, and apoptosis [168]. ATP released by ABCC6 and the nucleotides/nucleosides generated downstream by the ectonucleotidases NPP1 and CD73 regulates cellular signaling towards P2 (nucleotides) and P1 (Ado) receptors, which have a wide range of physiological influences that could well explain these other manifestations [124]. The primary advantage and benefit from therapies that directly aim at restoring ABCC6 function would be the potential rescue of the full spectrum of manifestations, not just calcification.
