CLN3 is a lysosomal/endosomal transmembrane protein essential for glycerophospholipid metabolism and lysosomal homeostasis. Functionally, CLN3 mediates microtubule-dependent anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes, and plasma membrane, regulating lysosomal pH, protein degradation, receptor-mediated endocytosis, and autophagy 1. Recent metabolomic studies reveal that CLN3 is specifically required for clearing glycerophosphodiesters (GPDs)—end products of glycerophospholipid catabolism—from lysosomes 2. GPD accumulation in CLN3-deficient lysosomes inhibits the phospholipases PLA2G15 and PLBD2, blocking downstream lipid catabolism and causing toxic lysophospholipid accumulation 3. Loss of CLN3 causes juvenile neuronal ceroid lipofuscinosis (Batten disease), an autosomal recessive neurodegenerative lysosomal storage disorder presenting with seizures, visual loss, and cognitive/motor decline 45. GPD accumulation in patient lysosomes correlates with disease severity, suggesting potential biomarker utility 6. Clinically, CLN3 disease remains untreatable, though emerging therapeutic approaches targeting TFEB activation show promise in preclinical models 7.