Mechanistic insights into glycerophospholipid metabolism in the lysosome

Phospholipid dysregulation is implicated in the pathogenesis of lysosomal storage disorders (LSDs). We found that glycerophosphodiesters (GPDs) accumulate in lysosomes derived from Batten disease models, a life-limiting LSD whose pathological mechanism remains elusive. GPDs are the degradation products of glycerophospholipid catabolism by phospholipases. Despite their fundamental role in membrane lipid turnover, the phospholipases that degrade glycerophospholipids in the lysosome are indeterminate. I will identify and characterize the exact machinery responsible for glycerophospholipid degradation in the lysosome. This will provide novel insights into the pathway of phospholipid metabolism and identify a potential therapeutic target in phospholipid-associated LSDs such as Batten disease.