While our findings do not support an essential role for Vps15/Vps34 in autophagy initiation and mTOR activation in these cell types, we uncover severe defects in autophagy maturation, lysosomal function, glycogen storage that in skeletal muscles cause AVM with sarcolemmal features, muscle weakness and lysosomal storage disease. This evidence concerns the gene PIK3R4 and lysosomal storage disease.