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Symptoms appear between 5 and 10\u00a0years of age, beginning with blindness and seizures, followed by progressive cognitive and motor decline, and premature death. Glial activation and impaired neuronal activity are early signs of pathology in the Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> mouse model of JNCL<\/jats:styled-content>, whereas neuron death occurs much later in the disease process. We previously reported that Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> microglia are primed toward a pro\u2010inflammatory phenotype typified by exaggerated caspase 1 inflammasome activation and here we extend those findings to demonstrate heightened caspase activity in the Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> mouse brain. Based on the ability of caspase 1 to cleave a large number of substrates that have been implicated in JNCL<\/jats:styled-content> pathology, we examined the functional implications of caspase 1 inflammasome activity by crossing Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> and caspase 1\u2010deficient mice to create Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup>\/Casp\u20101<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> animals. Caspase 1 deletion influenced motor behavior deficits and astrocyte activation in the context of CLN<\/jats:styled-content>3<\/jats:italic> mutation, since both were significantly reversed in Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup>\/Casp\u20101<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice, with phenotypes approaching that of wild\u2010type animals. We also report a progressive age\u2010dependent reduction in whisker length in Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> mice that was partially caspase 1\u2010dependent. However, not all CLN<\/jats:styled-content>3<\/jats:italic> phenotypes were reversed following caspase 1 deletion, since no significant differences in lysosomal accumulation or microglial activation were observed between Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> and Cln3<\/jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup>\/Casp\u20101<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice. Although the molecular targets of aberrant caspase 1 activity in the context of CLN<\/jats:styled-content>3<\/jats:italic> mutation remain to be identified, our studies suggest that caspase 1 may represent a potential therapeutic target to mitigate some attributes of CLN<\/jats:styled-content>3 disease.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p>This article is part of the Special Issue \u201cLysosomal Storage Disorders\u201d<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14480","type":"journal-article","created":{"date-parts":[[2018,6,6]],"date-time":"2018-06-06T06:54:57Z","timestamp":1528268097000},"page":"652-668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Caspase 1 activity influences juvenile Batten disease (CLN<\/scp>3) 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