With a more comprehensive knowledge of the structure of ASK1, its interactions with binding partners within the signalosome (e.g., from cryo-EM analysis of full-length ASK1 complexes) and on mechanisms of ASK1 regulation, together with the development of specific small-molecule ASK1 inhibitors, we anticipate significant advances in pharmacological interventions targeting ASK1 in several diseases, ranging from cancer to neurological disorders. The gene discussed is MAP3K5; the disease is nervous system disorder.