Although it is widely accepted the existence of putative estrogen receptors (ERs) localized at extranuclear domains in the brain, their molecular identity is still unclear. We have previously demonstrated in a murine septal cell line the existence of a membrane-related ER (mER) that participates in estrogen-mediated neuroprotection. To investigate the molecular structure of mER, we have used a battery of antibodies raised against different domains of the classical ERalpha to immunoblot with plasma membrane fractions from septal SN56 and hippocampal HT22 cell lines, and microsomal fractions of mouse septal and hippocampal tissues. The results confirmed that mER is the homologue of its intracellular counterpart ERalpha, suggesting the possibility that both nuclear and extranuclear receptors may share a common origin.