Kcnj10, also known as Kir4.1 or Kir1.2, encodes an ATP-sensitive inwardly-rectifying potassium channel. It is expressed in the brain, inner ear, and kidney [3]. In the kidney, it is involved in K⁺ recycling across the basolateral membrane in the late thick ascending limb, distal convoluted tubule (DCT), and connecting tubule/cortical collecting duct, and in generating negative membrane potential. It also regulates the Na-Cl cotransporter (NCC) expression via the Cl⁻-sensitive with-no-lysine kinase-SPAK pathway in the DCT [2].

In a mouse model with cerebellar heterozygous knockout of Kcnj10, mice presented dystonic posture, poor motor coordination, and motor learning ability, along with an elevated firing rate of deep cerebellar nuclei, suggesting that impaired Kir4.1 function might lead to abnormal neuronal excitability and contribute to paroxysmal kinesigenic dyskinesia (PKD) [1]. In another study, collecting system-specific deletion of Kcnj10 in mice predisposed them to thiazide-and low-potassium diet-induced hypokalemia, indicating that Kcnj10 in the collecting system contributes to the renal control of potassium homeostasis by regulating the epithelial sodium channel (ENaC) and the renal outer medullary potassium channel (ROMK) [4].

In conclusion, Kcnj10 plays essential roles in maintaining potassium homeostasis in the kidney and regulating neuronal excitability in the brain. Gene-knockout mouse models have been crucial in revealing its functions in diseases such as PKD and potassium-related renal disorders, helping to understand the underlying pathophysiological mechanisms.