Ubiquitination is a cellular process by which a small regulatory protein called ubiquitin is attached to a substrate protein. This protein modification can target the substrate for degradation through the proteasome, alter its cellular location, affect its activity or promote/prevent protein interactions. Ubiquitination requires several enzymes, namely: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBE4A encodes an additional E4 conjugation factor, required for efficient polyubiquitination that would enable proteasomal targeting of a substrate. The EF enzyme binds to the ubiquitin moieties of preformed conjugates and works in conjunction with E1, E2 and E3 to catalyze the ubiquitin chain assembly.