Unverricht-Lundborg disease (EPM1A), also known as Baltic myoclonus, is the most common form of progressive myoclonic epilepsy. It is inherited as an autosomal recessive trait, due to mutations in the Cystatin-B gene promoter region. Although there is much work on rodent models of this disease, there is very little published neuropathology in patients with EPM1A. Here, we present the neuropathology of a patient with genetically confirmed EPM1A, who died at the age of 76. There was atrophy and gliosis affecting predominantly the cerebellum, frontotemporal cortex, hippocampus and thalamus. We have identified neuronal cytoplasmic inclusions containing the lysosomal proteins, Cathepsin-B and CD68. These inclusions also showed immunopositivity to both TDP-43 and FUS, in some cases associated with an absence of normal neuronal nuclear TDP-43 staining. There were also occasional ubiquitinylated neuronal intranuclear inclusions, some of which were FUS immunopositive. This finding is consistent with neurodegeneration in EPM1A as at least a partial consequence of lysosomal damage to neurons, which have reduced Cystatin-B-related neuroprotection. It also reveals a genetically defined neurodegenerative disease with both FUS and TDP-43 related pathology.