For the regulation of MnSOD, AMPKα2 activity seemed somewhat more important than α1, a fact supported by the finding that addition of SOD to aortae from AMPKα2−/− mice can rescue endothelial dysfunction.5 Interestingly, the α2 subunit is thought to be the more sensitive to AMP,37 and this is consistent with our speculation that MTX activates AMPK by altering levels of AMP. The gene discussed is PRKAA2; the disease is endothelial dysfunction.