Mutations in eight different genes have been associated with neuronal ceroid lipofuscinoses (NCLs) in various dog breeds, providing canine models for the human NCL diseases. The document describes the pathways used to discover NCL mutations in dogs, including identifying affected dogs, histopathological analysis, whole genome sequencing, and candidate gene analysis. It focuses on the development of a Dachshund model of late-infantile NCL, where a mutation was identified in the TPP1 gene and an affected colony was established. This model is now being used to develop and test potential gene therapy, enzyme replacement therapy, and stem cell therapies for human late-infantile NCL.