Ubiquitination is an important mechanism through which three classes of enzymes act in concert to target short-lived or abnormal proteins for destruction. The three classes of enzymes involved in ubiquitination are the ubiquitin-activating enzymes (E1s), the ubiquitin-conjugating enzymes (E2s) and the ubiquitin-protein ligases (E3s). ZNRF2 (zinc and ring finger 2), also known as RNF202, is a 242 amino acid peripheral membrane protein that contains one RING-type zinc finger and localizes to the lysosome, as well as the endosome and the cell junction. Expressed at high levels in brain tissue, ZNRF2 is thought to function as an E3 ubiquitin-protein ligase that may be involved in the establishment and maintenance of neuronal transmission and plasticity. Upon DNA damage, ZNRF2 is subject to phosphorylation, probably by ATR or ATM.