WNK4 and hyperinsulinemic hypoglycemia, familial, 4: These side effects can be independent of volume status and plasma K+ concentration.[57] Because both Spak deficiency and inhibition of Spak kinase activity corrected the phenotype of PHA II due to Wnk4 mutation, specific inhibition of SPAK may be a plausible therapy for patients with salt-sensitive hypertension related to WNK4 activation.