CLN1 disease (infantile neuronal ceroid lipofuscinosis), is caused by mutations in the PPT1 gene. While the effects of PPT1 deficiency upon the central nervous system (CNS) are well documented, the extent to which tissues outside the CNS are affected remains unclear. In this study, we investigated whether PPT1 deficiency damages the peripheral nervous system (PNS), neuromuscular junction (NMJ) and skeletal muscle, and whether early systemic gene therapy can prevent these manifestations. Using the Ppt1⁻/⁻ (CLN1) mouse model, we assessed NMJ morphology, terminal Schwann cell (tSC) survival and nerve coverage, and skeletal muscle structure at 5 and 7 months of age. In an attempt to prevent these pathologies mice received systemic AAV9-CLN1 gene therapy during the early postnatal period via intravenous injection. Untreated Ppt1⁻/⁻ mice exhibited significant NMJ pathology, including progressive tSC loss, reduced NMJ innervation, and abnormal NMJ morphology. In parallel, we observed skeletal muscle atrophy, with decreased myofiber diameter and reduced myonuclear content, despite preserved sciatic nerve morphology. Systemic AAV9-CLN1 therapy partially rescued these phenotypes, preserving NMJ innervation and muscle fiber structure. These findings reveal peripheral NMJ and muscle abnormalities as previously unrecognized features of CLN1 disease and provide proof-of-concept that early systemic gene therapy can mitigate these effects. Our results highlight the presence of extra-CNS CLN1 pathologies and support the need for treatment strategies that address both CNS and peripheral targets to achieve optimal treatment outcomes.