PRR7 is a synaptic transmembrane adaptor protein with dual roles in neuronal and immune signaling. In neurons, PRR7 functions as a synapse-to-nucleus messenger that translocates to the nucleus following NMDA receptor activation 1. At the molecular level, PRR7 inhibits ubiquitination-mediated degradation of the transcription factor c-Jun by blocking E3 ligase SCF(FBW7), thereby increasing c-Jun phosphorylation and transcriptional activity 1. This mechanism promotes NMDA receptor-mediated excitotoxicity and neuronal apoptosis, processes implicated in neurodegenerative diseases including Alzheimer's disease and stroke 1. PRR7 localizes to the postsynaptic density where it directly binds PSD-95 and associates with NMDA receptor subunits 2. Beyond excitotoxicity, PRR7 acts as a Wnt inhibitor and is activity-dependently released via exosomes to eliminate excitatory synapses in neighboring neurons through a non-cell autonomous mechanism 3. In immune cells, PRR7 shows redundant roles in T cell receptor signaling and promotes apoptosis when overexpressed 4; however, PRR7 knockout mice exhibit largely normal T cell development and immune function 5, suggesting compensatory mechanisms. PRR7 is palmitoylated, facilitating its localization in lipid rafts 6.