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J Physiol. 2019 Jul;597(14):3511-3521. doi: 10.1113/JP276163. Epub 2019 Jun 11.

Leucine rich repeat kinase 2: a paradigm for pleiotropy.

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School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AP, UK.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.


The LRRK2 gene, coding for leucine rich repeat kinase 2 (LRRK2), is a key player in the genetics of Parkinson's disease. Despite extensive efforts, LRRK2 has proved remarkably evasive with regard to attempts to understand both the role it plays in disease and its normal physiological function. At least part of why LRRK2 has been so difficult to define is that it appears to be many things to many cellular functions and diseases - a pleiotropic actor at both the genetic and the molecular level. Gaining greater insight into the mechanisms and pathways allowing LRRK2 to act in this manner will have implications for our understanding of the role of genes in the aetiology of complex disease, the molecular underpinnings of signal transduction pathways in the cell, and drug discovery in the genome era.


LRRK2; Parkinson's disease; human genetics; pleiotropy


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