The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK

Renal outer medullary K + (ROMK) and large-conductance Ca 2+ -activated K + channel (BK), both regulated by the clathrin adaptor autosomal recessive hypercholesterolemia (ARH), play essential roles in maintaining potassium balance. Given the life-threatening risks of dyskalemia, it is unsurprising that their activity is controlled by multiple mechanisms, though not without physiological costs. We found that impaired ARH-mediated ROMK and BK internalization triggers activation of alternative potassium-conserving pathways in a sex-specific manner. In females, who are more prone to hypokalemia, this compensation involves thiazide-sensitive sodium-chloride cotransporter (NCC) upregulation, a key player in blood pressure regulation.