Peptidyl-prolyl cis-trans isomerase H (PPIH)

Peptidyl-prolyl cis-trans isomerase H (PPIH) is a member of the cyclophilin family of isomerases, functioning primarily as an enzyme that catalyzes the cis-trans isomerization of proline residues in oligopeptides, which accelerates protein folding[1][5][6]. PPIH is specifically associated with the spliceosome, where it forms complexes with pre-mRNA processing factors (such as PRPF3, PRPF4, and PRPF18) and contributes to spliceosomal assembly and activity[1][3][5]. Recent data show additional roles in regulating RNA methylation (notably m6A) and cell cycle progression by modulating gene expression, which in turn supports tumor cell proliferation and survival in cancers such as hepatocellular carcinoma[2]. PPIH possesses a single isomerase domain and may also act as a chaperone, mediating dynamic protein–protein interactions required for accurate pre-mRNA splicing[3]. Several alternative names exist, mostly reflecting its enzymatic activity or association with ribonucleoprotein complexes[1][3][5]. Cyclosporin A, a broad cyclophilin inhibitor, binds PPIH but does not block all of its functional protein interactions[3][7]. Altered expression of PPIH is associated with poor prognosis in certain cancers, and its essential role in splicing may pose therapeutic targeting challenges due to its involvement in general RNA processing in normal cells[2][5].

Other names

Peptidylprolyl isomerase HCYP20CYPHPPIase HCypHUSA-CYPCYP-20SnuCyp-20Rotamase HSmall nuclear ribonucleoprotein particle-specific cyclophilin HU-snRNP-associated cyclophilin SnuCyp-20USA-CyP SnuCyp-20Cyclophilin HPPIHMGC5016U-snRNP-associated cyclophilin SunCyp-20

Competitive inhibition of prolyl isomerase catalytic site (by cyclosporin A and related inhibitors) Not specifically therapeutically targeted; no approved or widely studied selective inhibitors for PPIH