CTSD (cathepsin D) is an aspartic-type lysosomal protease serving as a major intracellular degradative enzyme with broad disease relevance. Functionally, CTSD cleaves misfolded proteins including α-synuclein and amyloid precursor protein (APP) 1, with its activity critical for lysosomal protein homeostasis. The enzyme operates in multiple cellular compartments including lysosomes, endosomes, and extracellular spaces 2. In neurodegenerative diseases, CTSD deficiency impairs α-synuclein clearance in Parkinson's disease, promoting accumulation of pathological conformers 1. Genetic burden analysis implicated CTSD as a candidate susceptibility gene for Parkinson's disease risk through compromised lysosomal function 3. Beyond neurodegeneration, CTSD's N-glycosylation modifications regulate colorectal cancer liver metastasis by controlling ferroptosis-related proteins 4. In diabetes, circulating pro-CTSD from monocytes non-enzymatically triggers blood-brain barrier transcytosis via caveolin-mediated pathways, contributing to cognitive impairment 5. During liver fibrosis resolution, macrophage-derived CTSD enables extracellular matrix remodeling essential for fibrosis reversal 2. Collectively, CTSD represents a multifunctional protease whose dysregulation contributes to neurodegeneration, metastatic cancer, vascular complications, and impaired tissue remodeling, making it an attractive therapeutic target across multiple pathologies.