The convergence of these dysregulated upstream signals, encompassing energy sensing through AMPK, redox balance mediated by NOX4 and SIRT1, and developmental signaling via Wnt, upon a compromised Nrf2 node underscores the centrality of its failure in COPD pathogenesis [27,49,53,54]. The gene discussed is NOX4; the disease is chronic obstructive pulmonary disease.