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Target intelligence / Profile preview
Leucine-rich repeat kinase 2 (LRRK2)
- Target
- LRRK2
- Molecular classification
- Enzyme, Kinase
01
Overview
Leucine-rich repeat kinase 2 (LRRK2) is a large 2527-amino acid multi-domain protein (286 kDa) expressed mainly in the cytoplasm and associated with mitochondrial outer membranes, highly expressed in immune cells like monocytes, dendritic cells, and neutrophils. It contains armadillo repeats (ARM), ankyrin repeats (ANK), leucine-rich repeats (LRR), ROC GTPase domain, COR domain, serine/threonine kinase domain, and WD40 domain, enabling dual enzymatic activities as a kinase and GTPase. LRRK2 regulates diverse processes including Rab protein phosphorylation (e.g., Rab8A, Rab10), lysosomal homeostasis, microglial migration, phagocytosis via WAVE2, autophagy, mitochondrial function, and innate immunity. Pathogenic mutations (e.g., G2019S, R1441C, I2020T) increase kinase activity, promote ROS via NOX2 phosphorylation, impair mitophagy, enhance neuroinflammation, and are strongly linked to familial and sporadic Parkinson's disease, as well as immune disorders.
- Other names
- leucine-rich repeat protein kinase 2
02
Mechanism of action
Kinase inhibition, GTPase modulation
03
Biological functions
Signal transductionAutophagyPhagocytosisMitochondrial functionCytoskeleton dynamicsVesicular traffickingImmune responseCell migration
04
Disease associations
Neurodegenerative diseaseParkinson's diseaseInflammationInflammatory bowel diseaseLeprosySystemic lupus erythematosus
05
Safety considerations
Elevated kinase activity leading to ROS productionLysosomal dysfunctionAutophagy impairmentNeuroinflammation
06
Interacting drugs
LRRK2 kinase inhibitors
07
Biomarkers
LRRK2 G2019S mutationLRRK2 R1441C mutationLRRK2 I2020T mutationpRab10 levels
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