Cyclophilin (peptidyl-prolyl cis-trans isomerase family) (CYP (commonly CypA, CypB, CypC, CypD for isoforms))

Cyclophilins are a family of conserved enzymes possessing peptidyl-prolyl cis-trans isomerase activity, accelerating the interconversion of cis and trans forms of peptide bonds before proline residues[3][7]. This function is critical for proper protein folding, prevention of aggregation, and assembly of multidomain proteins. Cyclophilins are found throughout cellular compartments—cytosol, nucleus, mitochondria, and even secreted forms. They became widely studied after the discovery of their high-affinity binding to cyclosporin A, an immunosuppressive drug, and mediate CsA’s action by forming a ternary complex with calcineurin—this blocks T-cell activation and is the basis for CsA’s clinical use in transplantation and autoimmune diseases[3][5]. Beyond immunology, particular isoforms such as Cyclophilin D are central to cell death pathways via regulation of mitochondrial permeability transition pores[6]. Cyclophilins are also implicated in viral replication (HIV, HCV), cancer, neurodegeneration, cardiovascular disease, and inflammation, making them an attractive and versatile therapeutic target whose inhibition remains a key area of drug development[3][5][7]. Key structural features include a highly conserved β-barrel fold and PPIase active site, with specificity determined by side pockets in the structure and additional domains in multidomain isoforms[1][2][4].

Other names

Peptidyl-prolyl cis-trans isomeraseCYP (with isoform letters: CypA, CypB, CypC, CypD, etc.)Cyclophilin A/B/C/D/E (human gene symbols: PPIA, PPIB, PPIC, PPID, etc.)Cyclosporin A-binding protein

Inhibition of peptidyl-prolyl isomerase activity (by CsA and other inhibitors) Disruption of Cyclophilin-dependent protein folding and assembly Immunosuppression via inhibition of calcineurin with CsA-Cyclophilin complex