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Overexpression of GRK2 is linked to cardiovascular diseases, and its inhibition or deletion has been shown to be protective. The functions of GRK2 extend beyond G protein\u2010coupled receptor (GPCR) signaling, influencing non\u2010GPCR substrates as well. Increased GRK2 in heart failure (HF) initially may be protective but ultimately leads to maladaptive effects such as GPCR desensitization, insulin resistance, and apoptosis. The multifunctional nature of GRK2, including its action in hypertrophic gene expression, insulin signaling, and cardiac fibrosis, highlights its complex role in HF pathogenesis. Additionally, GRK2 is involved in mitochondrial biogenesis and lipid metabolism. GRK2 also regulates epinephrine secretion from the adrenal gland and its increase in circulating lymphocytes can be used to monitor HF status. 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