Leucine-rich repeat kinase 2:14-3-3 protein–protein interface (LRRK2:14-3-3 interface)

This target refers to the **protein–protein interaction interface between leucine-rich repeat kinase 2 (LRRK2) and 14-3-3 proteins**. LRRK2 is a large, multidomain protein kinase with GTPase activity implicated in familial and sporadic Parkinson’s disease. Binding of phosphorylated LRRK2 to 14-3-3 proteins stabilizes its localization and regulates its function; disruption of this interaction impacts LRRK2 activity, subcellular distribution, and participation in signaling complexes. LRRK2 modulates downstream signaling such as Rab GTPase phosphorylation and microtubule dynamics, affecting neuronal viability and inflammation. The LRRK2:14-3-3 interface is being explored as an indirect therapeutic target, primarily through kinase inhibition, to restore normal cellular function in disease settings.

Other names

LRRK2–14-3-3 interactionLeucine-rich repeat kinase 2 and 14-3-3 protein complexLRRK2 PPI with 14-3-3LRRK2:14-3-3 binding site

Inhibition of LRRK2 kinase activity, which can disrupt or modulate 14-3-3 binding Modulation of PPI to alter cytoskeletal interactions and localization