Huntingtin-interacting protein 2 (HIP2/LIG), is a E2 ubiquitin-conjugating enzyme, which accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, HIP2/LIG catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, while it does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Moreover, HIP2/LIG mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins.