The complete cDNA sequence of a novel gene, SCIRR69 (spinal cord injury and regeneration related no. 69 gene), was obtained by RACE technique. It codes for a protein of 521 amino acid residues homologous to human CREB3l2 (also known as BBF2H7) and mouse CREB3l2. The protein contains a basic DNA binding and leucine zipper dimerization (B-ZIP) motif and a hydrophobic region representing a putative transmembrane domain, similar to the structure of other CREB/ATF transcription factors. Monoclonal antibody against SCIRR69 was developed and could recognize the SCIRR69 protein in both native and denatured forms. Constructing of SCIRR69 fusion proteins with the GAL4 DNA-binding domain disclosed that SCIRR69 functioned as a transcriptional activator and its N-terminal 60 amino acids accounted for the activation ability. SCIRR69 resides in the cytoplasm of primary neurons, whereas neuron damage by incision led to the cleavage and translocation from the cytoplasm to the nucleus. These results suggest that SCIRR69 is activated by proteolytic cleavage at the transmembrane domain in response to neuron damage and its amino-terminal cytoplasmic domain translocates into the nucleus to activate the transcription of target genes.