GRK2

GRK2 (G protein-coupled receptor kinase 2) is a ubiquitously expressed serine/threonine kinase that functions as a central regulator of G protein-coupled receptor (GPCR) signaling through receptor phosphorylation, β-arrestin recruitment, receptor desensitization, and internalization^[1][2]. Mechanistically, GRK2 acts beyond canonical GPCR regulation by interacting with multiple signaling proteins, including Gαq, MAPK-associated pathways, and non-receptor substrates, thereby serving as a multifunctional signaling hub that integrates cellular responses to extracellular stimuli^[3][4]. Through these activities, GRK2 influences diverse biological processes such as inflammation, migration, metabolism, and cardiovascular homeostasis^[4][5]. In disease contexts, elevated GRK2 expression has been consistently associated with heart failure, cardiovascular dysfunction, obesity-related metabolic disorders, and insulin resistance, while genetic or pharmacological attenuation of GRK2 activity shows protective effects in experimental models^[5][6]. Compared with related isoforms, GRK2 belongs to the ubiquitously expressed GRK2 subfamily together with GRK3, yet exhibits distinct regulatory interactions and has emerged as the most extensively studied isoform in cardiovascular and metabolic pathophysiology^[1][5]. For experimental applications, GRK2 has attracted considerable interest as a therapeutic target, and multiple small-molecule inhibitors have been developed to suppress its kinase activity or interfere with its signaling functions, providing valuable tools for mechanistic studies and preclinical disease research^[6][7].