Deubiquitinases (DUBs) are enzymes used by cells to trim protein modifications made from the protein ubiquitin, and thereby regulate proteins. Malfunctioning of DUBs could lead to diseases, including cancer and neurodegenerative disorders. A protein called USP53 has been recently linked with progressive familial intrahepatic cholestasis, a hereditary liver disease in children, yet its mechanism of action has remained elusive. While its sequence made it part of a deubiquitinase family, previous attempt to detect catalytic activity had remained inconclusive. Now, a team has decoded the mode of action of USP53 and its related enzyme called USP54.