G protein-coupled receptor kinase 5 (GRK5)

G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase that phosphorylates activated GPCRs, leading to desensitization (via arrestin recruitment), receptor internalization, and modulation of downstream signaling, including biased agonism. It is widely expressed, especially in the heart, lung, and placenta. Beyond classical receptor regulation, GRK5 can phosphorylate non-GPCR substrates such as α-synuclein, mediating additional non-receptor signaling roles. GRK5 is a promising target in cardiovascular disease and neurodegeneration, with selective inhibitors (e.g., CCG215022) under preclinical investigation. Genetic variants in GRK5 affect drug responses and disease susceptibility, highlighting its relevance as a biomarker and therapeutic target. Regulation of GRK5 involves calcium/calmodulin-mediated conformational controls and localization dynamics[1][2][3].

Other names

GRK5GPRK5G protein-coupled receptor kinase GRK5FP2025

Inhibition of GRK5 activity, preventing GPCR desensitization and altering downstream signaling[3] Modulation of arrestin-mediated bias signaling pathways (potential for biased agonism)[2] Interference with phosphorylation of non-receptor substrates such as α-synuclein[1]