Regulation of LRRK2: insights from structural and biochemical analysis

Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein and its mutations can lead to Parkinson's disease. Recent studies on LRRK2 and homologue proteins have advanced our mechanistic understanding of LRRK2 regulation. Here, we summarize the available data on the biochemistry and structure of LRRK2 and postulate three possible layers of regulation, translocation, monomer-dimer equilibrium and intramolecular activation of domains.