CbCln3Δex7/8 cerebellar precursor cells represent the first genetically accurate neuron-derived culture model of JNCL. Homozygous CbCln3Δex7/8 cells express mutant battenin and JNCL-hallmark mitochondrial ATPase subunit c accumulation, upon aging of cells at confluency. Moreover, this is the first study to indicate recessive endosomal/lysosomal membrane trafficking defects and mitochondrial dysfunction that precedes subunit c deposition in an accurate JNCL model. Importantly, these defects are likely to be early events in the JNCL disease process and may particularly impact neuronal function.