USP46: a new piece of the memory puzzle?

Long-term potentiation (LTP) and long-term depression (LTD) are crucial for synaptic plasticity, and are driven by AMPA receptor (AMPAR) trafficking. Recent findings indicate that the ubiquitin-proteasome system, the main protein degradation machinery of the cell, plays a significant role in memory formation by regulating the induction and maintenance of LTP. Although previously suggested as a possibility, deubiquitination of mammalian AMPARs had not been demonstrated, and the search for an enzyme that mediates the processes continued. This Editorial Highlight discusses the relevance of a study published in the current issue of Journal of Neurochemistry, in which the authors Huo and collaborators now identified ubiquitin-specific peptidase 46 (USP46) as a specific AMPAR deubiquitinase.