ARH3 thus counteracts PARG by degrading PARG-generated free PAR chains induced by severe oxidative DNA damage (Mashimo et al., 2013), providing a potential therapeutic target not only for CONDSIAS patients, but also other forms of parthanatos-induced cell death, for instance in ischemic brain injury and other neurodegenerative illnesses (Mashimo et al., 2013, 2019). Here, ADPRS is linked to neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures.