Over the past years, several LRRK2 kinase inhibitors have been developed, including LRRK2-IN-1 , HG-10-102-01 , MLi-2 , PF-06447475 , and DNL201 and DNL151 which are the first two LRRK2 kinase inhibitors in clinical trials . However, all these inhibitors are ATP-competitive type 1 kinase inhibitors which preferably bind to the closed active conformation of LRRK2, leading to dephosphorylation of Ser935 and other biomarkers sites, LRRK2 aggregation, and mislocalization to microtubules . These unintended effects may interfere with vesicle trafficking and could underlie undesirable on-target side-effects observed on lungs and kidneys . Alternative LRRK2 targeting strategies, such as G2019S LRRK2 selective inhibitors , LRRK2 Type II inhibitors, LRRK2 dimerization inhibitors , GTPase inhibitors, antisense oligonucleotide , type 2 LRRK2 kinase inhibitors , and LRRK2 proteolysis targeting chimeras (PROTACs) , have therefore been proposed and are under active exploration.