CLDN19 encodes claudin-19, a tight junction protein that forms paracellular cation-selective channels essential for renal ion homeostasis 1. In the thick ascending limb of Henle's loop, CLDN19 coassembles with CLDN16 to facilitate paracellular magnesium and calcium reabsorption by establishing a lumen-positive transepithelial potential 2. The protein also functions as a paracellular barrier in peripheral nervous system Schwann cells and contributes to retinal pigment epithelium barrier properties during retinal development 3. Loss-of-function CLDN19 mutations cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), characterized by severe hypomagnesemia, hypercalciuria, nephrocalcinosis, and progressive renal failure typically progressing to kidney failure by the second to third decade of life 2. Approximately 60% of CLDN19 mutation carriers develop ocular abnormalities including retinal defects 4. Clinical phenotype shows significant intrafamilial variability; females progress to chr1 kidney disease stage 3 faster than males, and elevated baseline parathyroid hormone levels predict more severe renal decline 4. Currently, no curative therapies exist; kidney transplantation remains the only definitive treatment for FHHNC-related kidney failure 2.