Studies of mouse models carrying uromodulin mutations confirm that intracellular accumulation of mutant uromodulin leads to ER stress, induction of the unfolded protein response, and subsequent tubular damage and interstitial fibrosis—substantiating the gain of toxic function mechanism in ADTKD-UMOD [53]. This evidence concerns the gene UMOD and autosomal dominant medullary cystic kidney disease with or without hyperuricemia.