Leucine-rich repeat kinase 2 (LRRK2) is a complex, scaffolding protein containing ankyrin, leucine-rich and WD40 repeats, and a catalytic core with Ras-Of-Complex (ROC) GTPase and serine-threonine kinase activities.  LRRK2 belongs to the family of ROCOs, multidomain proteins identified in a wide range of species, from prokaryotes to eukaryotes including humans. ROCO proteins possess a ROC domain invariably followed by a C-terminus Of ROC (COR) domain likely involved in protein dimerization. ROCO proteins, including LRRK2, have been implicated in a variety of fundamental biological processes converging in cytoskeletal and vesicle dynamics. Nominated LRRK2 substrates are clustered within three major biological categories – (1) cytoskeleton dynamics, (2) vesicle-related processes and (3) protein transcription/translation - and there are robust functional indications linking LRRK2 with these processes. With regard to cytoskeleton dynamics, LRRK2 has been reported to phosphorylate a number of cytoskeletal-related proteins including tau, the tau kinase MARK1, tubulins, ARHGEF7, ezrin-radixin-moesin (ERM) and the Drosophila microtubule (MT)-binding protein Futsch.


1.Taymans JM,et al. Curr Neuropharmacol. 2016;14(3):214–225.