Batten disease protein CLN8 enables a non-canonical phospholipid synthesis pathway.

CLN8 enables an alternative glycerophospholipid synthesis pathway that produces BMP, which is essential for lysosomal lipid homeostasis, and its deficiency causes lipid accumulation.

• Why it matters: Understanding lysosomal lipid metabolism is crucial because its disruption is linked to neurodegenerative diseases like Batten disease, yet the pathways involved are not fully known.
• What they did: The study used tracer experiments in cells and mice to show that CLN8 catalyzes the acylation of glycerophosphoglycerol, leading to BMP formation, and that knockout models lack this pathway.
• The result: Loss of CLN8 impairs BMP synthesis, causes BMP deficiency, and results in phospholipid buildup in lysosomes, suggesting this pathway's role in disease mechanisms and potential therapeutic targets.