Abstract
β-Site amyloid precursor protein cleaving enzyme-1 (BACE1) is a central molecule in Alzheimer's disease (AD). It cleaves amyloid precursor protein (APP) to produce the toxic amyloid-β (Aβ) peptides. Thus, a novel BACE1 modulator could offer a new therapeutic strategy for AD. We report that C-type lectin-like domain family 4, member g (Clec4g, also designated as LSECtin) interacts with BACE1 in mouse brain and cultured cells. Overexpression of Clec4g suppressed BACE1-mediated Aβ generation, and affected the intracellular distribution of BACE1 but not its catalytic activity. These results highlight a novel role of Clec4g in negatively regulating BACE1 function.