Specifically phosphorylates the activated forms of G protein- coupled receptors (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:39138140, PubMed:40384633). Such receptor phosphorylation initiates beta-arrestin-mediated receptor internalization, and signaling events leading to their desensitization (PubMed:14976224, PubMed:16179383, PubMed:19306925, PubMed:19715378, PubMed:21799898, PubMed:23077507, PubMed:30284927, PubMed:39138140, PubMed:40384633). Phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (PubMed:19715378). Phosphorylates catecholamine-activated ADRB2 to regulate physiological cardiomyocyte contraction rate responses (By similarity). Also phosphorylates ligand-bound C3a and C5a anaphylatoxin receptors (C3AR1 and C5AR1, respectively), leading to receptor desensitization (PubMed:21799898, PubMed:23077507). Positively regulates ciliary smoothened (SMO) signaling pathway by mediating phosphorylation of SMO, facilitating SMO trafficking into the cilium and the stimulation of SMO activity (PubMed:39138140). Also positively regulates SMO signaling by mediating phosphorylation of GPR161, a key inhibitor SMO signaling, promoting ciliary export of GPR161 (PubMed:40384633). Key regulator of LPAR1 signaling (PubMed:19306925). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (PubMed:19306925). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (PubMed:19306925). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927). {ECO:0000250|UniProtKB:P21146, ECO:0000250|UniProtKB:Q99MK8, ECO:0000269|PubMed:14976224, ECO:0000269|PubMed:16179383, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:19715378, ECO:0000269|PubMed:21799898, ECO:0000269|PubMed:23077507, ECO:0000269|PubMed:30284927, ECO:0000269|PubMed:39138140, ECO:0000269|PubMed:40384633}. This is the function of Ensembl gene identifier ENSG00000173020 (GRK2, G protein-coupled receptor kinase 2).