While it is known that inappropriate expression of NOX4 can lead to redox imbalance and pathology (57), the NOX4/Nrf2-dependency of protective HO-1 induction by A-CRLPs reported here is wholly consistent with recent evidence in murine models that NOX4, when specifically coupled to Nrf2 activation, protects the heart during chronic pressure overload (58) and that endothelial NOX4 provides endogenous protection from atherosclerosis development (59). Here, NOX4 is linked to atherosclerosis.