BACE2 (Beta-secretase 2, Memapsin-1) is an aspartic protease and membrane glycoprotein that generates amyloid beta peptide by cleaving the amyloid precursor protein. It also functions in the melanogenesis of melanocytes by cleaving PMEL17, the luminal domain of which is released to form amyloid fibrils in the melanosome amyloid matrix. In the brain, BACE2 is thought to be involved in neuroinflammation, processing various substrates involved in inflammatory response such as VCAM1. In the mouse brain, it is found in populations of oligodendrocytes, neurons and astrocyte-like cells in lateral ventricles, and has normally low expression that increases during inflammation (Voytyuk, 2018). BACE2 is a target of inhibition therapies in Alzheimer’s disease due to its direct action to generate amyloid beta peptides, which aggravates symptoms and contributes to progression. In immunohistochemistry, BACE2 has generally low cytoplasmic positivity in the brain, muscle, gastrointestinal tissue, skin, the prostate and a few other tissues. References: Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10658-63, PMID: 23754390; Cytogenetics and Cell Genetics. 89 (3–4): 177–84, PMID: 10965118; Voytyuk et al. Life Sci Alliance. 2018 Feb 15;1(1):e201800026, PMID: 30456346; JCI Insight. 2019 Jan 10; 4(1): e123431, PMID: 30626751;