CREB3L2, a member of the CREB3 family of transcription factors, spans >120 kbp and is composed of 12 exons. We characterized a widely expressed transcript of CREB3L2 generated by an intronic polyadenylation site in intron 4 of the gene. It could be translated to a CREB3L2 variant which is localized both in the nucleus and the endoplasmatic reticulum. The protein retains the N-terminal transactivation domain but lacks the DNA-binding domain, the transmembrane domain and the C-terminal part. Experiments using a GAL4 DNA-binding domain fusion model showed that the transcript is a transactivator but it cannot exert its function through the CRE and ATF6 binding sites and has little effect on the GRP78 promoter. Whether this transcript has a cellular function or is targeted for degradation by nonsense-mediated RNA decay system of RNA surveillance is currently unknown.