The two most under-expressed proteins in NSCLC tissues, CAI and CAII, belong to a widespread family of 16 metallo-isoenzymes that catalyze the interconversion between carbon dioxide and the bicarbonate ion; these enzymes are involved in crucial physiological processes connected to respiration and transport of CO2/bicarbonate, in pH and CO2 homeostasis, and in many other metabolic reactions [38]. The gene discussed is CA1; the disease is non-small cell lung carcinoma.