Proteoglycans are protagonists in autophagy, lymphangiogenesis, and neurodegenerative diseases.

Proteoglycans (PGs) are specialized cell-surface and secreted proteins teeming with bioactivity. They have been the subject of fascinating research on autophagy, lymphangiogenesis, and neurodegenerative diseases. PG influence on autophagy extends to several disease domains, and their ability to alter autophagic processes has highlighted their suitability as therapeutic targets. PGs also display new functions by evoking protracted autophagy in lymphatic endothelial cells and inhibiting tumor and physiological lymphangiogenesis. The variable degree of PG sulfation and their ability to regulate growth-factor activities in the central nervous system has opened doors into novel therapeutic avenues including Alzheimer's and Parkinson's diseases. This review systematically integrates these diverse qualities of PGs while highlighting future directions towards clinical application.