Mixed lineage kinases are a family of protein kinases sharing two leucine zipper-like motifs, which are known to mediate protein dimerization, and a kinase domain whose primary structure is similar to both the tyrosine-specific and the serine/threonine-specific kinase classes. Members of the mixed-lineage kinase (MLK) family include MLK1, MLK2, MLK3 and dual leucine zipper kinase, also designated DLK. MLKs are expressed in neuronal cells where they are likely to interact between Rac1/Cdc42, MKK4 and MKK7 in death signaling. The human MLK1 gene maps to chromosome 14q24.3-q31 and is expressed in epithelial tumor cell lines of the colon, breast, and esophagus. The human MLK2 gene maps to chromosome 19 q13.2. and encodes a predicted 954 amino acid, src homology 3 (SH3) domain-containing protein. The human MLK3 gene maps to chromosome 11q13.1-13.3 and encodes a 847 amino acid, SH3 domain- and proline rich region-containing protein. Apoptosis mechanisms rely on MLKs as an upstream intermediate of mitochondrial cytochrome c release and caspase activation.