Leucine-rich repeat kinase 2 (LRRK2) (LRRK2)

Leucine-rich repeat kinase 2 (LRRK2) is a large, multi-domain protein encoded by the LRRK2 gene located at the genomic locus 12q12 (UniProt Q5S007). It functions as both a GTPase and a serine/threonine-protein kinase, playing a critical role in endolysosomal trafficking, autophagy, and immune response regulation (PubMed: 29127256). Mutations within this locus, particularly the G2019S substitution, are the most common genetic cause of Parkinson's disease, leading to a pathological gain-of-function in kinase activity (PubMed: 15514144). This overactivity is associated with neurodegeneration, making LRRK2 a primary target for therapeutic intervention. Current drug development strategies include small-molecule kinase inhibitors and antisense oligonucleotides designed to reduce LRRK2 activity or expression levels (PubMed: 32029640). Clinical trials are monitoring efficacy through biomarkers like phosphorylated Rab10 and urinary BMP levels. However, safety concerns persist regarding potential effects on the lungs and kidneys, as observed in preclinical studies (PubMed: 25644304).

Other names

DardarinPARK8RIPK7ROCO2Leucine-rich repeat serine/threonine-protein kinase 2

Kinase inhibition; Antisense oligonucleotide-mediated knockdown