The enzymatic activity of PNKP is involved in the repair of both DNA double strand-break (DSB) and single-strand break (SSB); impaired function can cause neurodevelopmental dysfunction (microcephaly, seizures, and developmental delay (MCSZ)) [84] and neurodegeneration (AOA4 and Charcot-Marie-Tooth disease (CMTD)) [11,36]. The gene discussed is PNKP; the disease is Charcot-Marie-Tooth disease.