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Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. All mentioned data are represented in the manuscript figures. Additional data will be made available upon request.

The interaction of the activating transcription factor 6 ATF6 , a key effector of the unfolded protein response UPR in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator DREAM is a potential therapeutic target in neurodegeneration.

Amyotrophic lateral sclerosis ALS is a neurodegenerative disorder with no cure, characterized by the progressive loss of motoneurons resulting in muscle denervation, atrophy, paralysis, and death. Encoded by four genes, KChIP1 to 4, KChIP proteins show distinct expression patterns in different organs as well as in different areas within the CNS [ 1 , 3 , 4 ] and have multiple functions [ 5 , 6 , 7 ], sometimes specific for the different family members recently reviewed in [ 8 , 9 ].

Importantly, changes in DREAM conformation are also induced upon binding of small molecules, like arachidonic acid [ 11 ], glinides [ 12 ] and some diaryl urea derivatives [ 13 ], which affects the interacting properties of DREAM and modifies its protein—protein interactions [ 10 ]. Whether this mechanism applies to other neurodegenerative diseases is currently not known.