More than 95% of the UMOD mutations associated with ADTKD are missense, often targeting cysteine residues and leading to the formation of uromodulin aggregates within the endoplasmic reticulum (gain-of-toxic function) with a sharp decrease of its excretion in urine. This evidence concerns the gene UMOD and autosomal dominant medullary cystic kidney disease with or without hyperuricemia.