CLN3 encodes a lysosomal/endosomal transmembrane protein that mediates intracellular transport between the Golgi network, endosomes, autophagosomes, lysosomes, and plasma membrane. It regulates multiple cellular processes including lysosomal pH, autophagy, receptor-mediated endocytosis, and synaptic transmission. At the plasma membrane, CLN3 regulates actin-dependent events such as filopodia formation and cell migration through the ARF1-CDC42 pathway. CLN3 loss-of-function mutations cause CLN3 disease (juvenile neuronal ceroid lipofuscinosis or Batten disease), the most prevalent form of childhood neurodegeneration 1. CLN3-deficient lysosomes accumulate glycerophosphodiesters (GPDs), the end products of glycerophospholipid catabolism 2. Recent evidence suggests GPDs act as potent inhibitors of lysosomal phospholipases, disrupting lipid homeostasis and causing toxic accumulation of lysophospholipids 3. Patients with CLN3 disease display progressive motor and cognitive decline, seizures, visual loss, and gastrointestinal dysfunction due to enteric nervous system degeneration 4. Clinical approaches under investigation include tamoxifen, an FDA-approved compound that reduces lysosomal Gb3 accumulation in CLN3 disease models through transcription factor EB (TFEB) activation 5, and systemic neonatal intravenous AAV9-hCLN3 gene therapy, which prevents bowel pathology in preclinical models 4. Glycerophosphoinositol in cerebrospinal fluid shows promise as a disease biomarker 2.