We demonstrated that CypA is upregulated in human CCA samples; CypA expression correlates with a malignant cell growth phenotype in CCA cell lines; inhibiting CypA expression reduces CCA cell proliferation and migration in vitro, with the effects on proliferation likely mediated by reduced enzymatic activity and that the ERK1/2 pathway may be involved; overexpression of CypA enhances cell proliferation; and, finally, that suppression of CypA reduces tumor size and cell proliferation in vivo. Here, MAPK3 is linked to cholangiocarcinoma.