CLCNKA encodes a voltage-gated chloride channel that functions as a homodimeric anion-selective transporter with selectivity for chloride over bromide, nitrate, and iodide 12. The channel contains two independent fast gates controlling each subunit and a slow common gate regulating both simultaneously, displaying linear current-voltage relationships when complexed with the regulatory subunit Barttin (BSND) 123. CLCNKA mediates transepithelial chloride transport in the thin ascending limb of Henle's loop, essential for generating the hypertonic medullary interstitium required for urine concentration 4. The channel also conducts chloride currents in the inner ear's stria vascularis to establish the endocochlear potential necessary for normal hearing 435. Clinically, CLCNKA variants associate with salt-sensitive hypertension; polymorphisms rs848307 and rs1739843 upstream of CLCNKA significantly correlate with blood pressure changes after sodium loading 67. Loss-of-function mutations cause Bartter syndrome 4B with neonatal sensorineural hearing loss, though some patients present with hearing loss as the dominant phenotype without renal involvement 8. Mutations in CLCNKA combined with CLCNKB deletions or individual CLCNKA mutations result in complex polyuro-polydipsic syndromes with electrolyte wasting 9. Additionally, CLCNKA variants associate with dilated cardiomyopathy risk 10.