Homozygous deletion of the mitochondrial transcription factor A (Tfam) gene within DA neurons causes mtDNA depletion and ETC deficiency, accompanied by classical PD features including age-related L-DOPA responsive motor dysfunction, mild cognitive impairment, intraneural inclusions, and rapidly progressive severe DA degeneration (163, 164, 165). The gene discussed is TFAM; the disease is Parkinson disease.