PNKP and Huntington disease: It is important to note that the DDR kinase also play important role in mediating DNA repair processes in the neurons by triggering phosphorylation-dependent activation of DNA damage repair proteins such as BRCA1, p53, PNKP, Ku70, ligase IV, etc. Therefore, one must consider the possibility that therapeutic approaches for HD aiming to block the DDR kinases with small molecule inhibitors may lead to impaired DNA repair in neurons, resulting in adverse consequences.