A Rutgers University study uncovers the role of the protein cypin in regulating synaptic content through K63-linked polyubiquitination (polyUb), a post-translational modification previously studied mainly in cancer contexts. Cypin modulates proteasome subunit levels and activity, altering protein composition at neuronal synapses in both developing neurons and adult mice. These findings, published in Science Advances, provide mechanistic insight into synaptic protein regulation essential for cognitive functions and suggest new therapeutic avenues targeting cypin to enhance memory and neural connectivity.