A 45-year-old male with bipolar disorder on chronic lithium therapy presents with polyuria (8 L/day) and polydipsia. Serum osmolality is 295 mOsm/kg and serum sodium is 142 mEq/L. A water deprivation test shows minimal increase in urine osmolality (from 150 to 165 mOsm/kg), which does not improve further after intravenous desmopressin (DDAVP). The structure marked **D** in the diagram (Aquaporin-2) fails to respond appropriately to ADH signaling. Which of the following best explains the pathophysiology in this patient?