PPIA (peptidylprolyl isomerase A) is a peptidyl-prolyl cis-trans isomerase that functions as a protein folding chaperone and plays critical roles in cancer progression and cellular stress responses. The protein stabilizes key oncogenic factors, particularly NRF2, by physically binding to prevent ubiquitin-mediated degradation, thereby promoting lung cancer progression 1. PPIA acts through direct protein-protein interactions, with structural studies revealing it binds to a trans-proline 174-harboring hydrophobic sequence in target proteins 1. In breast cancer, NQO1 stabilizes PPIA by preventing oxidation at cysteine residue C161, leading to CD147 activation and subsequent neutrophil recruitment and NET formation that drives lung metastasis 2. PPIA also functions as a secreted factor that modulates immune responses and can serve as a receptor for microbial adhesin proteins 2. The protein has emerged as a therapeutic target, with FDA-approved cyclosporin A effectively disrupting PPIA-NRF2 interactions and suppressing NRF2-hyperactivated cancer cell growth 1. Additionally, PPIA inhibition sensitizes multiple myeloma cells to proteasome inhibitors and reduces SARS-CoV-2 replication when pharmacologically targeted 34. Multiple studies identify PPIA as a potential biomarker for hepatocellular carcinoma diagnosis 5.