Ask1 (apoptosis signal-regulating kinase 1), a serine/threonine kinase, is a member of the MAPKKK family that constitutes the JNK and p38 (MAPK) cascades. Members of this family are activated by physiological and cytotoxic stresses and induce various stress responses including apoptosis. Specifically, Ask1-MAPK cascades have been shown to be involved in endoplasmic reticululum (ER) stress-induced apoptosis and in neuronal cell death. Studies suggest that ER stress-induced apoptosis plays critical roles in the pathogenesis in some neurodegenerative diseases including Alzheimer's, Parkinson's, polyglutamine (polyQ), amyotrophic lateral sclerosis (ALS) and Prion diseases. However, the regulation and function of Ask1 in neuronal cell death remains to be fully elucidated. In addition to playing a role in ER stress-induced apoptosis, Ask1 is also thought to be important in cytokine-induced apoptosis, and may also have functions other than apoptosis including roles in cell survival and differentiation. Structurally, human Ask1 has a serine/threonine kinase domain in the middle of the molecule. The kinase domain is evolutionarily conserved from nematode to human. A threonine residue with the activation loop of the kinases domain (Thr838 of human Ask1) is essential for Ask1 activation. There are two coiled-coil domains, one in the N-terminal and the other in the C-terminal domain. The coiled-coil domain in the C-terminal domain has been shown to be required for homo-oligomerzation.