The extremely rare human genetic disease spinocerebellar ataxia with axonal neuropathy (SCAN1) is associated with an H493R mutation in TDP1 [60] that reduces the rate of hydrolysis of tyrosyl-DNA bonds by about 25-fold, and also dramatically increases the lifetime of a transient intermediate wherein TDP1 is covalently linked to the DNA 3′-terminus [61]. The gene discussed is TDP1; the disease is spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1.