 Strategies to inhibit GRK2 include using small molecules (including Paroxetine and Compound-101) and using gene therapy approaches utilizing regulatory domains of GRK2 (particularly overexpressing the carboxy terminal pleckstrin-homology (PH) domain that binds the G protein βγ-subunit complex and inhibits GRK2 activation (often called the “βARKct”), or just a peptide from this PH domain).GRK2 and the related GRK3 can interact with heterotrimeric G protein subunits resulting from GPCR activation, both to be activated and to regulate G protein signaling pathways.GRK2 and GRK3 share a carboxyl terminal pleckstrin homology (PH) domain that binds to G protein βγ subunits, and GPCR activation of heterotrimeric G proteins releases this free βγ complex that binds to GRK2/3 to recruit these kinases to the cell membrane precisely at the location of the activated receptor, augmenting GRK activity to regulate the activated receptor.