Umod+/− mice exhibited renal failure at 24 weeks (elevated BUN and serum creatine levels), decreased body weight, renal fibrosis, reduced urinary uromodulin levels and accumulation of uromodulin in the ER, which activates unfolded protein response mechanisms and triggers ER stress-dependent cell death in renal tubule epithelial cells. Here, UMOD is linked to acute kidney injury.