The ERK/MAPK signaling pathway is crucial for memory formation and maintenance across species. Although much is known about ERK phosphorylation, recent hypotheses suggest a potential role for ERK/MAPK dimerization, primarily described in cancer research. However, no studies have demonstrated this mechanism in the nervous system or explored its implications. Our group has recently shown that this mechanism is critically involved in memory reconsolidation in mice. In the crab N. granulata, two-trial long-term memory (2t-LTM) requires ERK phosphorylation. Preliminary results from our group suggest that ERK dimerization would be evolutionarily conserved in crabs and may also regulate 2t-LTM. However, detecting ERK dimerization in its nervous system has proven challenging. To address this, we developed a simple ex vivo assay to evaluate the effects of different stimuli and of the dimerization inhibitor DEL-223792 (DEL) on this molecular mechanism. Together, these findings and the methodological approach provide a useful platform to investigate ERK dimerization and its role in memory processes. This experimental framework could also be employed to test different drugs or neuroactive compounds.