The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial matrix enzyme complex that functions as the primary link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the irreversible conversion of pyruvate into acetyl-CoA. The E1 enzyme of the PDH complex is made up of a heterotetramer of two α and two β subunits. The E1-α subunit (PDH-E1α) contains the E1 active site and plays a key role in the function of the PDH complex. The PDH complex is regulated by phosphorylation and dephosphorylation of PDH-E1α. The gene encoding for PDH-E1α maps to chromosome Xp22.12, and a 20bp deletion in the last exon of this gene is sufficient to cause PDH deficiency, which causes a broad range of symptoms including the development of seizures, mental retardation and spasticity, as well as intermittent episodes of lactic acidosis associated with cerebellar ataxia.