receptor desensitization, whether heterologous or homologous, may contribute to human pathology. for example, excessive desensitization due to the overexpression of grk2 leads to the loss of β-adrenergic receptor signaling in hearts (see adrenergic receptor#β receptors]. β-blockade and direct inhibition of grk2 restores β-adrenergic receptor signaling and has been proven beneficial for the treatment of chronic heart failure in humans and animal models. on the other hand, inactivating mutations of grk1 lead to faulty rhodopsin receptor desensitization and are linked to oguchi disease, a non-progressive form of night blindness. similarly, single nucleotide polymorphisms in grk4γ or that cause an increase in g protein-coupled receptor kinase (grk) activity cause serine phosphorylation and uncoupling of the d1 receptor from its g protein effector grk4. this impairs the kidney's renal sodium reabsorption, diuresis, and excretion of sodium and water; it is associated with genetically based essential hypertension in humans and animal models.