MLK4 belongs to the MAP kinase subfamily. The MLK family members are characterized by the presence of signature sequences of Ser/Thr and Tyr kinases within their catalytic domain. The MLK1-4 contains an aminoterminal Src-Homology (SH3) domain, followed by the kinase domain, a leucine-zipper region, and a Cdc42/Rac-interactive binding (CRIB) motif. MLK4 expressed in two splicing variants, MLK4α and MLK4β. The difference of these two isoforms is located in their C-terminal portion. The negative effect of MLK4 on LPS-induced ERK and JNK activation could be very important in controlling the level of cytokine expression, and thus maintaining the balance of inflammatory responses.