KCNJ16 encodes Kir5.1, an inwardly rectifying potassium channel that plays a critical role in renal electrolyte homeostasis and acid-base balance. The channel functions as a heteromeric complex with Kir4.1 (KCNJ10) at the basolateral membrane of distal kidney tubules, mediating potassium recycling essential for sodium reabsorption 1. Loss-of-function mutations in KCNJ16 cause hypokalemic tubulopathy and deafness (HKTD), an autosomal recessive disorder characterized by hypokalemic metabolic acidosis, salt wasting, and sensorineural hearing loss 2. The channel's dysfunction disrupts voltage-dependent electrolyte transporters and leads to metabolic impairments including altered TCA cycle and lipid metabolism 3. Beyond the kidney, Kir5.1 is expressed in pancreas and thyroid, suggesting broader physiological roles 4. Animal models demonstrate that KCNJ16 deficiency causes seizure susceptibility, impaired ventilatory responses, and brainstem neuroinflammation 56. Clinically, HKTD patients face severe complications including cardiogenic shock and brain edema, emphasizing the need for early diagnosis 2. Therapeutic approaches using statins show promise in addressing metabolic dysfunction associated with KCNJ16 deficiency 3.