In this severe disorder, characterized by ataxia and intellectual disability, among other neurological symptoms, the E3 ubiquitin ligase UBE3A/E6AP (E6-associate protein) is nonfunctional due to mutations or deletions in the maternal allele, and concomitant epigenetic silencing of the paternal allele (i.e., parental imprinting) (102–105). Here, UBE3A is linked to cerebellar ataxia.