Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics

G protein-coupled receptors (GPCRs) represent humans' most prominent family of membrane proteins. In contrast, G protein-coupled receptor kinases (GRKs) play a pivotal role in the rapid desensitization of GPCRs. GRK2 is a particularly significant member of the GRK family. Recent studies have demonstrated that GRK2 primarily regulates immune cell function and homeostasis through receptor desensitization. Over the past decade, substantial progress has been made in elucidating the role of GRK2 in various human diseases. Notably, GRK2 is implicated in a range of autoimmune disorders, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), Sjögren's syndrome (SS), autoimmune myocarditis, hepatitis, and Graves' disease. Furthermore, emerging research has expanded our understanding of GRK2's involvement in cancer biology. Comprehensive investigations into the biological and pathological functions of GRK2 have facilitated the development of therapeutic strategies aimed at targeting the GRK2 signaling pathway in cancer, inflammation, and autoimmune diseases. Promising results have been observed with targeted biologics in preclinical and clinical trials. This review aims to elucidate the multifaceted role of GRK2 in immune function, autoimmune diseases, and cancer to uncover the remaining complexities associated with this kinase. A thorough understanding of GRK2 may position it as a potent therapeutic target in treating inflammation and cancer.