LRRK2

LRRK2 (Leucine Rich Repeat kinase 2) is a cytoplasmic protein of 2527 amino acids. This protein is widely expressed in Substantia Nigra (SN) specially in the A9 Dopaminergic neurons (A9 DA). Other regions in the brain where LRRK2 has also been identified include cortex, hippocampus, straitum and cerebellum. Peripheral organs where the existence of LRRK2 has been detected include Heart, Placenta, Kidney, Lung, Skeletal Muscle, Pancreas etc. Subcellular localization of LRRK2 is observed in Golgi, Mitochondira and endosomal vesicles.

As a protein, LRRK2 has both GTPase activity and kinase activity encoded by the same molecule. This is one of the very few proteins found in the human genome which has both the activities in the same gene. The kinase function of LRRK2 has been of utmost importance in PD as it has been observed that enhanced kinase activity of LRRK2 mutants (G2019S, R1441C) leads to neurodegenation and cell death. The kinase domain has reasonale sequence homology to MLK (Mixed Lineage Kinase) subfamily of MAPKKK proteins. How does PD-associated mutant LRRK2 deviate from normal function remains to be elucidated in detail which will in turn help us deduce the normal function of LRRK2 in brains.