Although the toxicity of high poly-ADPr levels has been suggested as the cause of neurodegeneration in patients with ARH3 deficiency14 in agreement with the current model of mono-ADPr as a primer for poly-ADPr,12,13 toxic accumulation of mono-ADPr readers on chromatin might constitute a key factor underlying this inherited neurodegenerative disorder.26 Here, ADPRS is linked to inherited neurodegenerative disorder.