Heparan Sulfate Proteoglycan (HSPG) mediated signaling has been shown to play a role in a variety of cellular pathways and processes through binding of ligands and cell-to-cell crosstalk. Namely, HSPGs have been shown to modulate signals utilizing the major growth regulatory pathway, the Phosphoinositide-3-kinase (PI3K) pathway, which is known to down-regulate the initiation and propagation of autophagy signaling. Autophagy is the cell’s recycling mechanism for damaged cellular components and organelles, and we have previously shown increased autophagy markers when HSPG biosynthesis has been compromised. We therefore hypothesize that functioning HSPG signaling is required for the down-regulation of autophagy, mediated by the PI3K/mTOR pathway. Using two biosynthetic mutants and a mutant effecting a global sulfatase regulator, this relationship has been examined using a variety of stains and confocal imaging of Drosophila melanogaster tissues. Additionally, a relationship between HSPG signaling, autophagy, and neurodegeneration has been investigated through light microscopy and a novel algorithm.