Like all AGC kinases, GRKs use ATP to add phosphate to Serine and Threonine residues in specific locations of target proteins.

Phosphorylated serine and threonine residues in GPCRs act as binding sites for and activators of arrestin proteins.

For example, GRK1 is regulated by the calcium sensor protein recoverin: calcium-bound recoverin binds directly to GRK1 to inhibit its ability to phosphorylate and desensitize rhodopsin, the visual GPCR in the retina, in light-activated retinal rod cells since light activation raises intracellular calcium in these cells, whereas in dark-adapted eyes, calcium levels are low in rod cells and GRK1 is not inhibited by recoverin.

[12] Polymorphisms in the GRK4 gene have been linked to both genetic and acquired hypertension, acting in part through kidney dopamine receptors.

[13] In humans, a GRK5 sequence polymorphism at residue 41 (leucine rather than glutamine) that is most common in individuals with African ancestry leads to elevated GRK5-mediated desensitization of airway beta2-adrenergic receptors, a drug target in asthma.

[15] In the mouse, GRK6 regulation of D2 dopamine receptors in the striatum region of the brain alters sensitivity to psychostimulant drugs that act through dopamine, and GRK6 has been implicated in Parkinson's disease and in the dyskinesia side effects of anti-parkinson therapy with the drug L-DOPA.

[18][19] GRKs also regulate cellular responses independent of their kinase activity.