Objective Downstream regulatory element antagonist modulator (DREAM), as a multifunctional Ca2+ binding protein, binds with specific DNA sequence to regulate gene expression and with Kv4.2 or presenilins outside the nucleus to regulate membrane excitability and calcium homeostasis, respectively.Two main isoforms of DREAM (A and B) were produced by alternative splicing.Our study is to observe the characterization of DREAM isoforms expression and distribution in astrocytes and neurons.Methods Expression of DREAM A and B mRNA in primary culture of neural cells (astrocytes, GABAergic neuron and glutamatergic neuron) was measured by real time PCR.Subcloned DREAM isoform A or B in pIRES2-EGFP vectors and the plasmids were transfected into astrocytes to observe their subcellular localization.Results We found that both DREAM A and B are present in all neural cells studied.Isoform A was in a higher level in glutamatergic neuron whereas isoform B was in a higher level in astrocyte.Isoform A showed a diffusible distribution and isoform B appeared mainly localized in the ER.The mRNA levels of these two isoforms were measured in these neural cells at different age.We found that isoform A showed the highest level in older but isoform B showed the highest level in younger cultures.We confirmed these developmental changes in tissue of cerebral cortex and cerebellum.Conclusion These data suggest that DREAM A is the major isoform in mature cells and can function as a transcriptional repressor.DREAM B is mainly localized in ER and may play a role in the early stage of development.