LRRTM3 (leucine rich repeat transmembrane neuronal 3) is a synaptic adhesion protein that plays a critical role in amyloid-beta (Aβ) production and Alzheimer's disease pathogenesis. The protein promotes amyloid precursor protein (APP) processing by BACE1, with siRNA knockdown reducing Aβ40, Aβ42, and sAPPβ secretion by up to 60% in cultured cells and primary neurons 1. LRRTM3 co-localizes and co-immunoprecipitates with both APP and BACE1 in early endosomes, where BACE1 processing of APP occurs 2. The protein is expressed nearly exclusively in nervous system regions affected in Alzheimer's disease, including the dentate gyrus 1. LRRTM3 maps to chromosome 10 at a linkage peak associated with late-onset Alzheimer's disease (LOAD) risk and elevated plasma Aβ42 levels 1. Genetic association studies have identified significant multilocus genotypes within LRRTM3's 5'UTR-Intron 1 region associated with LOAD risk 2. However, LRRTM3-deficient mice show no differences in Aβ levels or APP processing compared to wild-type mice, suggesting the protein may not be essential for Aβ production in vivo 3. Beyond Alzheimer's disease, LRRTM3 has been implicated in sarcopenia through large-scale Mendelian randomization studies 4.