G protein-coupled receptor kinase 4 (GRK4) is an enzyme that is encoded by the GRK4 gene in humans. This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most similar to GRK5 and GRK6. G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an arrestin protein to the receptor. Arrestin binding to a phosphorylated, active receptor prevents receptor stimulation of heterotrimeric G protein transducer proteins, blocking their cellular signaling and resulting in receptor desensitization. Moreover Arrestin binding to a phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Consequently the GRK/arrestin system serves as a signaling switch for G protein-coupled receptors. GRK4 is most highly expressed in the testes, with lower amounts found in the brain, kidney and other tissues. It exists in four alternatively-spliced variants. Polymorphisms in the GRK4 gene have been linked to both genetic and acquired hypertension, partly acting through kidney dopamine receptors.