Here we describe a patient with an atypical and exceptionally early-onset form of CLN5-associated NCL who also carries a variably penetrant dominant mutation (p.Gly517Val) in POLG1, a nuclear gene encoding the catalytic subunit of mitochondrial DNA polymerase, which is critical for maintenance of mtDNA copy number and mitochondrial physiology. This evidence concerns the gene POLG and neuronal ceroid lipofuscinosis.