APBB3 (amyloid beta precursor protein binding family B member 3) is a protein adapter that modulates amyloid-beta precursor protein (APP) internalization and participates in cholesterol homeostasis pathways relevant to neurological disease. As a member of the Fe65 protein family, APBB3 interacts with the intracellular domain of APP 1 and functions as a molecular adaptor containing phosphotyrosine-interaction domains and a WW domain 2. APBB3 tethers APP to lipoprotein receptors at the cytoplasmic domain 3, playing a role in the cerebral cholesterol shuttle pathway implicated in Alzheimer's disease pathogenesis. The protein exhibits antiapoptotic properties through a conserved C-terminal TR2(L) sequence that confers resistance to TNF-mediated cell death 4. Notably, APBB3 overexpression increases secretion of beta-amyloid peptides 5, linking it directly to amyloid pathology. APBB3 expression is differentially regulated in mood disorders; it was identified among 12 genes showing altered expression in depressed patients with bipolar disorder or major depressive disorder, with mRNA levels correlating with neuroimaging abnormalities in brain regions including the amygdala and hippocampus 6. These findings suggest APBB3 may bridge molecular-level immune dysfunction to neurological disease phenotypes through APP metabolism and amyloid-beta generation.