BACE1 (beta-secretase 1) is an aspartic-type endopeptidase that catalyzes the rate-limiting step in amyloid-β (Aβ) generation through proteolytic cleavage of amyloid precursor protein (APP) at the N-terminus of the Aβ peptide sequence, releasing soluble APP and a C-terminal fragment subsequently processed by γ-secretase 1234. BACE1 expression is tightly regulated through leaky scanning and reinitiation mechanisms involving multiple upstream AUGs in its 5' UTR, maintaining relatively low baseline expression 5. Beyond APP processing, BACE1 modulates neuronal IL-6 signaling by cleaving gp130, the IL-6 receptor component, thereby controlling membrane-bound versus soluble gp130 levels and neuronal survival pathways 6. BACE1 phosphorylation at Thr252 by GSK3β enhances its enzymatic activity and alters ligand recognition, with structural differences between human and rat BACE1 potentially explaining clinical trial failures of inhibitors 7. Beyond Alzheimer's disease pathology, BACE1 participates in diverse age-related conditions including metabolic dysfunction, vascular disease, and cancer, where BACE1 inhibition can reprogram tumor-promoting macrophages toward tumor-suppressive phenotypes 89. Genetic studies show BACE1 polymorphisms associate with seizure susceptibility and may confer protective effects in specific populations 1011.