Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable cation channel activated by ADP-ribose or reactive oxygen species. In human, a major transcript of 6.5 kb is expressed in various tissues, whereas a minor transcript of 5.5 kb is detected only in striatum (caudate nucleus and putamen). We found that the 5.5-kb shorter transcript is transcribed from the intron 4 of the TRPM2 gene and encodes the striatum short form protein (SSF-TRPM2) with 1289 amino acid residues as compared to the long form protein (LF-TRPM2), in which the N-terminal 214 amino acid residues are removed. The SSF-TRPM2 protein still maintained H2(O2)-induced Ca2+ influx activity. In addition, we found that the major transcripts in human and mouse start from a novel 5' non-coding exon; however, we could not detect any striatum short transcript in mouse brain. These new findings are invaluable to further study the regulation of TRPM2 gene expression and to examine the possible involvement of the TRPM2 gene in the pathophysiology of bipolar disorder.