<h4>Background</h4>Development of therapies for CLN3 disease, a rare pediatric lysosomal storage disorder, has been hindered by the lack of etiological insights and translatable biomarkers to clinics.<h4>Methods</h4>We used a deep multi-omics approach to discover blood-based biomarkers using longitudinal serum samples from a porcine model of CLN3 disease. The gene discussed is CLN3; the disease is lysosomal storage disease.