FK506-binding protein 5 (FKBP5 (or FKBP51))

FK506-binding protein 5 (FKBP5), commonly known as FKBP51, is a large immunophilin with peptidyl-prolyl cis-trans isomerase (PPIase) activity, encoded by the human FKBP5 gene[1][2][9]. It acts as a key regulator of steroid hormone receptor complexes by binding to the heat shock protein 90 (Hsp90) and modulating the sensitivity of glucocorticoid, progesterone, and mineralocorticoid receptors[1][3][9]. Structurally, FKBP51 has two FKBP domains and a tetratricopeptide repeat (TPR) domain that facilitates extensive protein-protein interactions within cellular chaperone complexes[2][9]. FKBP51 is a recognized molecular target in diseases like cancer (particularly melanoma), stress-related psychiatric disorders, chronic pain, and obesity, owing to its crucial functions in protein folding, stress response, and signal transduction pathways[3][6]. It is targeted by immunosuppressant drugs such as tacrolimus and sirolimus, as well as selective small-molecule inhibitors (e.g., SAFit analogs) that disrupt its regulatory interactions[6]. Elevated FKBP51/FKBP5 expression or genetic variation can serve as biomarkers for disease susceptibility and therapeutic response, but interventions must carefully consider potential safety concerns related to immune and hormone system modulation[6].

Other names

FKBP51FKBP5FKBP-51immunophilin FKBP5151-kDa FK506-binding protein

Inhibition of peptidyl-prolyl isomerase activity, Disruption of steroid receptor complex formation, Selective blocking of FKBP51 through ligand binding, Modulation of Hsp90 chaperone complex, Inhibition of FKBP51-steroid receptor and protein-protein interactions