LRRK2

About LRRK2

LRRK2 Leucine Rich Repeat Kinase 2 on chromosome 12q12 encodes a large multidomain protein with both kinase and GTPase activity, involved in vesicle trafficking, lysosomal function, and immune signaling. Pathogenic LRRK2 variants are the most common known cause of autosomal dominant Parkinson disease. The G2019S variant is found in a small fraction of people with apparently sporadic Parkinson disease in many populations, but is much more frequent among Ashkenazi Jewish and North African Berber populations. Penetrance is incomplete and increases with age, so many carriers never develop the disease. LRRK2 associated Parkinson disease closely resembles typical late onset Parkinson disease, with asymmetric tremor and a good response to levodopa, although Lewy body pathology is variable. Most pathogenic variants increase LRRK2 kinase activity, making the kinase an attractive drug target, and LRRK2 kinase inhibitors are in clinical development. The gene was identified in 2004, and its protein is also called dardarin, from the Basque word for tremor. Common LRRK2 variants have also been associated with Crohn disease and leprosy, pointing to roles in immunity.