Using dual-luciferase reporter assay system, our previous study showed that LI2, significantly increased AP-1 transcriptional activity. Sub-cellular localization showed that GFP-LI2 fusion protein is diffusely distributed in the cytoplasm, with some highly concentrated spots around the nucleus, suggesting that LI2 protein has a physiological role in cytoplasm. Overexpression of LI2 significantly increased AP-1 transcriptional activity. Moreover, LI2 significantly promoted transcriptional activity of Elk1 and c-jun, which might, at least partly, be associated with activated ERK1/2 and JNK/SAPK signaling pathway. These data suggest that LI2 is a novel MAPK regulating protein.