ARC (activity-regulated cytoskeleton-associated protein) is a master regulator of synaptic plasticity that functions through multiple interconnected mechanisms. Structurally, ARC is derived from ancient retrotransposons and self-assembles into virus-like capsids that encapsulate and transfer RNA between neurons via extracellular vesicles, representing a novel intercellular communication pathway in the nervous system 1. Functionally, ARC mediates activity-dependent synaptic strength regulation by promoting AMPA receptor (AMPAR) endocytosis through clathrin-mediated pathways, thereby maintaining synaptic homeostasis and enabling both long-term potentiation and depression 2. At the molecular level, ARC is phosphorylated by CaMKII and acts as a hub protein interacting with multiple effectors including NMDAR subunits and PI3K adapters to activate AKT signaling 3. This NMDAR-Arc-PI3K-mTORC2-AKT pathway mediates input-specific metaplasticity that protects potentiated synapses from depotentiation, thereby enabling memory updating and protecting against cognitive interference 3. Clinically, Arc dysfunction is implicated in Alzheimer's disease, where the NMDAR-AKT transduction complex is reduced in affected postmortem brain tissue 3. Arc's flexible, context-dependent signaling supports its role as a specialized master organizer critical for information storage, long-term memory formation, and cognitive function 4.