UCHL1 is a deubiquitinating enzyme highly expressed in neurons that regulates cellular ubiquitin homeostasis and protein degradation 1. As a cysteine-type deubiquitinase, UCHL1 hydrolyzes ubiquitin C-terminal peptide bonds to maintain stable monoubiquitin pools essential for the ubiquitin-proteasome and autophagy-lysosome pathways 2. UCHL1 deubiquitinates and stabilizes multiple substrates including BACE1, EGFR, HIF1A, and HSPA8, thereby regulating amyloid-beta production, receptor signaling, hypoxia responses, and chaperone-mediated autophagy 3. The enzyme modulates redox homeostasis and cellular senescence through ferroptosis regulation 3. Pathologically, UCHL1 dysregulation associates with neurodegenerative diseases and Parkinson disease, though a common S18Y polymorphism shows no significant association with Parkinson risk in Asian populations 4. UCHL1 elevation promotes neuroendocrine carcinoma progression, triple-negative breast cancer, pulmonary arterial hypertension via AKT1 stabilization, and keloid pathogenesis through IGF-1-Akt/mTOR signaling 5678. UCHL1 inhibitors show therapeutic promise across these conditions, with LDN-57444 demonstrating efficacy in preclinical models.