Peptidyl-prolyl cis-trans isomerase FKBP1B (FKBP1B) (FKBP1B)

Peptidyl-prolyl cis-trans isomerase FKBP1B, commonly known as FKBP12.6, is a member of the immunophilin family that serves as a critical regulatory subunit for the ryanodine receptor 2 (RyR2) in cardiac muscle (UniProt: P68108). It binds to RyR2 with high affinity, stabilizing the channel in its closed state during diastole to prevent pathological calcium leaks from the sarcoplasmic reticulum (PubMed: 10747031). This interaction is vital for maintaining synchronized calcium release and normal cardiac rhythm. In diseases like heart failure and catecholaminergic polymorphic ventricular tachycardia (CPVT), the dissociation of FKBP1B from RyR2—often triggered by PKA-mediated hyperphosphorylation or oxidative stress—results in diastolic calcium sparks and life-threatening arrhythmias (PubMed: 11056525). Drugs like Tacrolimus and Sirolimus bind to FKBP1B, which can inadvertently cause its dissociation from RyR2, potentially leading to cardiotoxicity (PubMed: 15133451). Experimental compounds known as rycals (e.g., S107, ARM210) are currently being investigated for their ability to enhance the binding of FKBP1B to RyR2, thereby restoring calcium homeostasis in cardiac and skeletal muscle disorders (PubMed: 18390990). Beyond the heart, FKBP1B is involved in regulating insulin secretion in pancreatic beta cells and has been linked to age-related cognitive decline (PubMed: 15034564). The protein also possesses peptidyl-prolyl isomerase activity, which facilitates protein folding by catalyzing the rotation of proline peptide bonds. Overall, FKBP1B represents a significant therapeutic target for stabilizing calcium signaling in various chronic conditions.

Other names

FKBP12.6FK506-binding protein 1B12.6 kDa FK506-binding proteinPPIase FKBP1BhFKBP12.6Immunophilin FKBP12.6

Stabilization of the ryanodine receptor (RyR2) channel complex to prevent diastolic calcium leak and inhibition of peptidyl-prolyl cis-trans isomerase activity.