LRRK2 (Leucine-Rich Repeat Kinase 2)

Category: biomarker

A kinase enzyme whose gain-of-function mutations are the most common genetic cause of Parkinson's disease. A major drug target for disease modification.

Mechanism Detail

LRRK2 mutations (most commonly G2019S) increase kinase activity, leading to excessive phosphorylation of Rab GTPases. This disrupts vesicular trafficking, lysosomal function, and autophagy — key pathways in dopaminergic neuron survival. LRRK2 also plays roles in immune cell function and inflammation.

Clinical Status

LRRK2 kinase inhibitors (DNL151/BIIB122, LOXO-340) are in Phase II clinical trials. ASO approaches targeting LRRK2 mRNA are in early clinical development. LRRK2 mutation carriers represent ~1-2% of PD cases.

Relevant Diseases

Relevant Therapies

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