>Up to 90% of the total proteome of a single neuron resides in dendrites and axons. Local proteasomal function is thus essential for synaptic homeostasis as wel

>Up to 90% of the total proteome of a single neuron resides in dendrites and axons. Local proteasomal function is thus essential for synaptic homeostasis as well as plasticity. Here, we found an unexpected abundance of free 19S regulatory particles near synapses. We discovered that these free 19S particles deubiquitylate important Lys63-ubiquitylated synaptic proteins such as AMPARs. The dynamics of Lys63 ubiquitylation and deubiquitylation potently regulated synaptic transmission. The excess of the free 19S proteasome particles present in dendrites thus represents an interesting example of a subcomplex of a multiprotein machine performing a moonlighting function near synapses, in this case as an independent “editor” of a synaptic ubiquitin code.