Abstract/Summary

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 a genetic and 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 for drug discovery in the genome era. The human LRRK2 gene, coding for a multidomain/multiactivity enzyme, acts as a pleiotropic disease locus - with tentacles extending into leprosy (left panel), inflammatory bowel disease (bottom panel), and Parkinson's disease (right panel). Image of an octopus by Gvlielmi Rondeletii and human terminal ileum by Michael Frank derived from the Wellcome collection under a creative commons license (image references L0060568 and A0001468), image of mycobacterium leprae derived from the Centres for Disease Control public health image library (image reference PHIL_2123, in the public domain), image of a parkinsonian patient derived from William Gowers Diseases of the Nervous System (image in the public domain).2