A study in today's Cell, shows how the loss of E3 ubiquitin ligase can cause Angelman syndrome, a genetic disorder that causes developmental problems in children. More than 10 years ago, researchers found that Angelman was caused by a single gene mutation, but could not explain the mechanism. Harvard's Michael Greenberg and his colleagues found that the loss of Ube3A interferes with the brain's ability to use environmental experiences to fine-tune neuronal circuits.