CTSD (Cathepsin D) is a lysosomal aspartyl protease of the peptidase C1 family that functions to degrade and also activate various intracellular proteins, hormones and growth factors such as VEGFC and VEGFD. Mutations in this gene are involved in the pathogenesis of several diseases, including breast cancer and possibly Alzheimer disease. Mutations and deficiency in CTSD lead to neuronal ceroid-lipofuscinosis (NCL). Loss of CTSD expression has been found to cause oxidative damage to pericytes in the brain, increasing permeability of the blood brain barrier and allowing peripheral blood mononuclear cells to infiltrate in lysosomal storage diseases and NCL. In immunohistochemistry of normal tissue, CTSD has granular cytoplasmic positivity throughout the body. References: The Journal of Biological Chemistry. 1989. 264 (23): 13403–6, PMID: 2760027; Critical Reviews in Oncology/Hematology. 68 (1): 12–28, PMID: 18396408; Brain. 2006 Jun;129(Pt 6):1353-6, PMID: 16738059; Alzheimer's and Dementia. 2009. 5(4), DOI: 10.1016/j.jalz.2009.04.796; Mol Cell Neurosci. 2015 Jan;64:51-60, PMID: 25496868