[5] ARC mRNA is localized to activated synaptic sites in an NMDA receptor-dependent manner,[6][7] where the newly translated protein is believed to play a critical role in learning and memory-related molecular processes.

[8] Arc protein is widely considered to be important in neurobiology because of its activity regulation, localization, and utility as a marker for plastic changes in the brain.

Dysfunction in the production of Arc protein has been implicated as an important factor in understanding various neurological conditions, including amnesia,[9] Alzheimer's disease, Autism spectrum disorders, and Fragile X syndrome.

[23] Also important for translocation of cytoplasmic Arc mRNA to activated synapses is an 11 nucleotide binding site for heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2).

[5] Following transcription, Arc mRNA is transported out of the nucleus and localized to neuronal dendrites[11] and activated synapses,[25] a process dependent on the 3' UTR,[21] polymerization of actin,[26] and ERK phosphorylation.

Subsequent efforts produced homozygous knockout mice by targeting the entire Arc gene rather than portions of the coding region, eliminating dominant negative effects.

These animals proved viable and exhibit no gross malformations in neuronal architecture, but express higher levels of the GluR1 subunit and increased miniature excitatory postsynaptic currents (mEPSCs) in addition to displaying deficiencies in long-term memory.