Our lab recently reported that the reduced abundance of nicotinamide dinucleotide (NAD+) in CS cells (patient-derived fibroblasts) and mice are associated with key CS phenotypes.7 NAD+ is a critical cofactor for several enzymes involved in mitochondrial biogenesis, mitophagy, and energy metabolism.8 It is likely that persistent DNA damage, observed in CS, constitutively activates poly-ADP ribose polymerase 1 (Parp1), which in turn depletes the cellular pool of NAD+. The gene discussed is PARP1; the disease is Cowden syndrome 1.