E3 ubiquitin ligases can be classified into three subfamilies. First is RING E3s, which act as scaffolding molecules to bring ubiquitin-charged E2 enzymes in close contact with their substrates. Second is HECT E3s, which catalyze the transfer of ubiquitin to their own cysteine residues and subsequently to substrates. And the third subfamily, RING-Between-RING (RBR) E3s, which include PARKIN and ARIH1, and mechanistically behave as hybrids between RING and HECT.