The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal lysosomal storage disorders characterized by progressive neurodegeneration. While much of the current research has focused on the thalamocortical system, cerebellum and spinal cord, patients with NCL also experience symptoms such as dysphagia, cardiac dysfunction, and autonomic instability—suggesting overlooked involvement of the brainstem. Indeed, despite its central role in coordinating motor, sensory, and autonomic functions, the brainstem remains poorly studied in NCL. In this study, we performed a comprehensive histological analysis of brainstem pathology in mouse models of CLN1 (Ppt1⁻/⁻), CLN2 (Tpp1R207X/R207X), and CLN3 (Cln3Δex7/8) diseases. Using immunofluorescece staining and stereological methods, we assessed key pathological features including accumulation of lysosomal storage material (SCMAS), astrocytosis (GFAP), microglial activation (CD68), and neuronal loss (Nissl staining) across multiple brainstem nuclei. At disease end stage, all three models exhibited marked glial activation and storage accumulation. These changes were most pronounced in functionally critical nuclei, such as the facial (VII), vagus (X), hypoglossal (XII), and spinal trigeminal (V) nuclei, as well as the reticular formation and nucleus tractus solitarius. Our findings demonstrate that brainstem involvement is a consistent and underappreciated feature across multiple forms of NCL, although its precise nature and extent varies between forms. This pathology likely contributes to key clinical symptoms and reflects distinct patterns of regional vulnerability in CLN1, CLN2, and CLN3 disease. A better understanding of how these changes evolve across the disease course will be essential for developing therapeutic strategies that address both forebrain and brainstem dysfunction in NCL.