Molecular Classification
Enzyme, Serine/Threonine Protein Phosphatase
Other Names
Protein Phosphatase 3, PP3, CaN
Disease Roles
Organ transplant rejectionAutoimmune diseasesNeurodegenerative diseases

Calcineurin Overview

Calcineurin is a highly conserved, calcium (Ca²⁺)- and calmodulin-dependent serine/threonine protein phosphatase that plays a central role in cellular signal transduction, especially in immune function and cardiovascular physiology. It is a heterodimer composed of a catalytic subunit (Calcineurin A) and a regulatory subunit (Calcineurin B). Calcineurin dephosphorylates specific substrates in response to increased intracellular Ca²⁺ levels, with a key function being the activation of T cells via NFAT dephosphorylation. It is a target for immunosuppressant drugs like cyclosporin A and tacrolimus, used to prevent organ transplant rejection and treat autoimmune diseases. Dysregulation of calcineurin is implicated in neurodegenerative and cardiovascular diseases.

Mechanism of Action

Calcineurin inhibitors (cyclosporin A and tacrolimus) bind to cyclophilin or FKBP12, respectively, and the resulting complex inhibits calcineurin activity.

Biological Functions

Signal transduction
Immune activation
T-cell signaling
Vascular regulation
Cardiac regulation
Neural regulation
Synaptic plasticity
Calcium signaling modulation

Disease Associations

Organ transplant rejection
Autoimmune diseases
Neurodegenerative diseases
Parkinson’s disease
Synucleinopathies
Cardiovascular disease

Safety Considerations

  • Immunosuppression-related side effects (e.g., increased risk of infection, nephrotoxicity)
  • Potential for neurotoxicity in some contexts
  • Aberrant activation/inhibition can be harmful depending on the specific disease context

Interacting Drugs

Cyclosporin A
Tacrolimus (FK506)