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In contrast, G protein\u2010coupled 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), Sj\u00f6gren\u2019s syndrome (SS), autoimmune myocarditis, hepatitis, and Graves\u2019 disease. Furthermore, emerging research has expanded our understanding of GRK2\u2032s 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. 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