Defective nicotinamide adenine dinucleotide (NAD+) metabolism is involved in various diseases. A study in Nature Metabolism identifies the cytosolic mitochondrial-RNA sensing system as a mediator that links NAD+ deficiency to kidney disease in humans and mice.Defective nicotinamide adenine dinucleotide (NAD+) metabolism is involved in various diseases. A study in Nature Metabolism identifies the cytosolic mitochondrial-RNA sensing system as a mediator that links NAD+ deficiency to kidney disease in humans and mice.