CUL4A and hypertensive disorder: The pathological significance of an impairment of GRK2 degradation by the CRL4AGβ E3 ligases, including CRL4AGβ3, is supported by the finding that Cul4a mutant mice accumulate higher levels of Grk2 protein and develop cardiac hypertrophy [26], hypertension and weakened heart function that can be partially rescued by the deletion of Grk2 (Figure 3).