Based on limited published evidence, C22orf39 negatively regulates long-term potentiation and modulates adult synaptic plasticity. It stabilizes RTN4 isoform A/Nogo-A interactions with receptors, inhibiting postsynaptic AMPA receptor clustering. Upon neuronal stimulation, C22orf39 is degraded at synapses, reducing RTN4 signaling and permitting AMPA receptor clustering. C22orf39 expression is silenced during MYC-driven hepatocarcinogenesis in liver stem cells, suggesting potential tumor suppressor function 1.