Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system (By similarity). ARC protein is released from neurons in extracellular vesicles that mediate the transfer of ARC mRNA into new target cells, where ARC mRNA can undergo activity-dependent translation (By similarity). ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons (By similarity). Acts as a key regulator of synaptic plasticity: required for protein synthesis-dependent forms of long-term potentiation (LTP) and depression (LTD) and for the formation of long-term memory (PubMed:29264923, PubMed:24094104, PubMed:31151856). Regulates synaptic plasticity by promoting endocytosis of AMPA receptors (AMPARs) in response to synaptic activity: this endocytic pathway maintains levels of surface AMPARs in response to chronic changes in neuronal activity through synaptic scaling, thereby contributing to neuronal homeostasis (PubMed:17088213, PubMed:20211139, PubMed:20228806). Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses (PubMed:23791196). Accumulates at weaker synapses, probably to prevent their undesired enhancement (By similarity). This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material (By similarity). Required to transduce experience into long-lasting changes in visual cortex plasticity and for long-term memory (PubMed:17088210, PubMed:20228806). Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1 (PubMed:22036569). In addition to its role in synapses, also involved in the regulation of the immune system: specifically expressed in skin-migratory dendritic cells and regulates fast dendritic cell migration, thereby regulating T-cell activation (PubMed:28783680). Homooligomer; homooligomerizes into virion-like capsids (PubMed:31151856). Interacts with SH3GL1/endophilin-2, SH3GL3/endophilin-3 and DNM2/DYN2 (By similarity). Interacts with CAMK2B (in the kinase inactive state); leading to target ARC to inactive synapses (By similarity). Interacts with PSEN1 (PubMed:22036569). Interacts with GRIN2A and GRIN2B; inhibiting homooligomerization (By similarity). Forms virion-like extracellular vesicles that are released from neurons (By similarity). Enriched in postsynaptic density of dendritic spines (By similarity). Targeted to inactive synapses following interaction with CAMK2B in the kinase inactive state (By similarity). Accumulation at weaker synapses may be required to prevent their undesired enhancement (By similarity). Associated with the cell cortex of neuronal soma and dendrites (By similarity). Associated with the sperm tail (PubMed:12493697). Expressed in brain and testis (PubMed:12493697). In primary visual cortex, detected in all cortical layers with the exception of layer 5: present at highest level in layers 2/3 and 4, the predominant sites of ocular dominance plasticity (at protein level) (PubMed:20228806). Also expressed in skin-migratory dendritic cells (PubMed:28783680). Ubiquitously expressed in early mouse embryos (PubMed:10727859). Detectable in brain from postnatal week 1, in testis from postnatal week 3. Arc expression is regulated at transcription, post-transcription and translation levels (PubMed:19116276, PubMed:24094104). Expression is induced by neuronal and synaptic activity (PubMed:19116276, PubMed:24094104). Ubiquitinated by UBE3A, leading to its degradation by the proteasome, thereby promoting AMPA receptors (AMPARs) expression at synapses. Palmitoylation anchors the protein into the membrane by allowing direct insertion into the hydrophobic core of the lipid bilayer. Phosphorylation at Ser-260 by CaMK2 prevents homooligomerization into virion-like capsids by disrupting an interaction surface essential for high-order oligomerization (PubMed:31151856). Phosphorylation by CaMK2 inhibits synaptic activity (PubMed:31151856). Mice show deficits in several forms of long-term memory formation including spatial and fear-related learning, conditioned taste aversion as well as long-term object recognition (PubMed:17088210). They show enhanced early-phase but impaired late-phase long-term potentiation (LTP) as well as impaired long-term depression (LTD). Neurons lacking Arc show an increase in surface levels of AMPA receptors (PubMed:17088210). In the visual cortex, mice are impervious to the effects of deprivation or experience: mice do not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation (PubMed:20228806). Although mice exhibit normal visual acuity, baseline ocular dominance is abnormal and resemble that observed after dark-rearing (PubMed:20228806). Mice also show schizophrenia-related phenotypes characterized by deficits in sensorimotor gating, cognitive functions, social behaviors and amphetamine-induced psychomotor responses (PubMed:27524619). Divergent alterations between the prefrontal cortex and striatal dopaminergic system that capture aspects of schizophrenia-related neuropathophysiology are observed (PubMed:27524619). Knockout mice show a relative loss of high-frequency electroencephalogram activity in hippocampus, as well as a decrease in phase locking of spikes to electroencephalogram oscillations (PubMed:27038743). Widely used as activity-dependent neuronal marker to identify recently activated neurons in behavioral studies. Belongs to the ARC/ARG3.1 family. Genetic disruption of the protein-coding gene was initially reported to cause early embryonic lethality (PubMed:10727859). However, only a partial deletion of the coding region was performed, leading to dominant-negative effects (PubMed:10727859). A complete deletion of the coding region later showed that mice are viable and display deficits in several forms of long-term memory formation (PubMed:17088210).