Tyrosyl-DNA phosphodiesterase 1 (TDP1) is an enzyme that participates in the repair of DNA strand breaks associated with topoisomerase 1 (Top1) complexes. TDP1 catalyzes the removal of Top1 from DNA via the hydrolysis of the phosphodiester bond between the tyrosine residue of Top1 and the 3’ phosphate of DNA. Removal of Top1 is then followed by DNA repair. TDP1 has been proposed to play more general roles in DNA damage repair independent of the Top1 complex. TDP1 has been shown to associate with DNA ligase IIIalpha, a component of the DNA single-stranded break repair (SSBR) machinery. It is also able to remove glycolate from 3’-phosphoglycolate termini of double-stranded breaks and a variety of other 3’- adducts. Defects in TDP1 are associated with spinocerebellar ataxia autosomal recessive with axonal neuropathy (SCAN1), a disease associated with peripheral axonal motor and sensory neuropathy and distal muscular atrophy.