LRRK2
Leucine-rich repeat kinase 2
Also known as: LRRK2, PARK8, dardarin
Biology & Mechanism
LRRK2 is a multidomain kinase with roles in vesicular trafficking, autophagy, and inflammatory signaling. It is expressed in microglia and macrophages, and gain-of-function mutations (most commonly G2019S) are the most common genetic cause of Parkinson's disease. In microglia, LRRK2 regulates lysosomal function, cytokine secretion, and responses to pathogen-associated molecular patterns. LRRK2 inhibitors are in clinical trials for Parkinson's disease.
Open Questions
- —What is the specific contribution of microglial LRRK2 to neurodegeneration versus neuronal LRRK2?
- —Can cell-type-selective LRRK2 inhibition be achieved for CNS versus peripheral immune cells?
- —Does LRRK2 activity modulate alpha-synuclein-induced microglial activation?
Sources
- Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease (2004)
Last reviewed: June 1, 2026