The characterization of differentially expressed proteins (control vs. CF, F508del heterozygous vs. F508del homozygous, PS vs. PI, normal/mild vs. moderate/severe lung function impairment) showcased nine CF diagnosis biomarkers (CUTA, ARG1, EZR, AGA, FLNA, MAN1A1, MIA3, LFNG, SIAE) and seven CF severity biomarkers (ARG1, GPT, MDH2, EML4 (F508del homozygous), MGAT1 (pancreatic insufficiency), TOLLIP, IGJ (lung function impairment)) candidates as well as potential markers of CFTR phenotypic rescue to be further investigated for clinical relevance. The gene discussed is MDH2; the disease is cystic fibrosis.