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Most forms present early in life and eventually lead to premature death. Typical pathological changes include neuronal accumulation of autofluorescent, periodic acid\u2010Schiff\u2010 and Sudan black B\u2010positive lipopigments, as well as marked loss of neurons in the central nervous system. Here, we describe a 19\u2010month\u2010old Schapendoes dog, where clinical signs were indicative of lysosomal storage disease, which was corroborated by pathological findings consistent with NCL. Whole genome sequencing of the affected dog and both parents, followed by variant calling and visual inspection of known NCL genes, identified a missense variant in <jats:italic>CLN6<\/jats:italic> (c.386T&gt;C). The variant is located in a highly conserved region of the gene and predicted to be harmful, which supports a causal relationship. The identification of this novel <jats:italic>CLN6<\/jats:italic> variant enables pre\u2010breeding DNA\u2010testing to prevent future cases of NCL6 in the Schapendoes breed, and presents a potential natural model for NCL6 in humans.<\/jats:p>","DOI":"10.1111\/age.13457","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:14:55Z","timestamp":1718237695000},"page":"612-620","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuronal ceroid lipofuscinosis in a Schapendoes dog is caused by a missense variant in <i>CLN6<\/i>"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8474-6624","authenticated-orcid":false,"given":"Kim K. 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