MAGEL2 and Angelman syndrome: Preclinical studies on gene-based interventions have demonstrated the promise of targeted approaches for modulating gene levels, especially for imprinting disorders such as Angelman syndrome (Meng et al., 2015; Wolter et al., 2020); however, in the case of truncating mutations in MAGEL2, future gene-based therapy efforts will need to take careful considerations when attempting to activate the silent maternal copy along with possibly targeting the existing pathogenic truncated MAGEL2 species through techniques such as proteolysis-targeting chimeras (Schapira et al., 2019).