We and others have not only validated that defective CFTR-mediated ROS-TG2 pathway drives the crosslinking of Beclin-1, which results in the accumulation of misfolded ΔF508-CFTR into p62+HDAC6+ aggresome bodies leading to autophagy dysfunction, but we have also demonstrated the key central role of autophagy in regulating CF pathogenesis and exacerbations [42,58,149,150]. This evidence concerns the gene CFTR and cystic fibrosis.