Peptidylprolyl isomerase A (PPIA), also known as cyclophilin A (CypA) or rotamase A is an enzyme that in humans is encoded by the PPIA gene on chromosome 7. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to regulate many biological processes, including intracellular signaling, transcription, inflammation, and apoptosis. Due to its various functions, PPIA has been implicated in a broad range of inflammatory diseases, including atherosclerosis and arthritis, and viral infections. Structure PPIA is an 18 kDa, 165-amino acid long cytosolic protein. Like other cyclophilins, PPIA forms a β-barrel structure with a hydrophobic core. This β-barrel is composed of eight anti-parallel β-strands and capped by two α-helices at the top and bottom. In addition, the β-turns and loops in the strands contribute to the flexibility of the barrel. Its active site is a hydrophobic pocket that binds peptides containing proline. Cyclosporine can bind this pocket to inhibit the protein’s enzymatic activity. Function This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate protein folding. Generally, PPIases are found in all eubacteria and eukaryotes, as well as in a few archaebacteria, and thus are highly conserved. Of the 18 known human cyclophilins, PPIA is the most abundantly expressed isozyme. In particular, PPIA is predominantly expressed in the nucleus and cytoplasm of the cell, where it partakes in intracellular signaling, protein transport, and transcription regulation. In hemopoietic cells, subcellular localization of PPIA from the nucleus to the cytoplasm has been observed during c-Jun N-terminal kinase- and serine protease-dependent microtubule disruption. This localization has been correlated with G2/M arrest, indicating that the protein's PPIase function may be regulated by microtubule dynamics during the cell cycle. PPIA has also been associated with the mitochondria. Moreover, the enzyme participates in inflammatory and apoptotic processes in extracellular settings. In the presence of reactive oxygen species (ROS), vascular smooth muscle cells (VSMCs), monocytes/macrophages, and endothelial cells (ECs) secrete PPIA to induce an inflammatory response and mitigate tissue injury. PPIA may also activate Akt and NF-κB signaling, resulting in the upregulation of Bcl-2, an antiapoptotic protein, and thus preventing apoptosis in ECs in response to oxidative stress. PPIA may also regulate ERK1/2, JNK, p38 kinase, Akt, and IκB signalling pathways through activating the CD147 receptor. PPIA-mediated