APBA3 (amyloid beta precursor protein binding family A member 3) is a cytoplasmic protein that functions as a modulator of amyloid-beta precursor protein (APP) processing and cellular metabolism. The protein contains phosphotyrosine interaction and PDZ domains enabling protein-protein interactions 1. APBA3 enhances hypoxia-inducible factor-1 (HIF-1) activity in macrophages by binding to and inhibiting factor inhibiting HIF-1 (FIH-1), thereby suppressing FIH-1's ability to modify HIF-1α and maintaining ATP production via glycolysis 2. This HIF-1 regulatory function is critical for macrophage metabolic function, as knockdown of APBA3 reduces glycolysis and ATP production 2. In Alzheimer's disease pathology, APBA3 expression is altered in choroid plexus tissue and is downregulated in neurons exposed to beta-amyloid in the presence of sensitizing nicotinic receptors, suggesting involvement in early-stage Aβ-induced neurotoxicity 34. Additionally, DNA methylation of APBA3 is dysregulated in borderline personality disorder and correlates with psychotherapy response, identifying it as a potential epigenetic biomarker for treatment outcomes 5. Hypertension-associated changes in APBA3 expression in aging hippocampus may contribute to late-onset Alzheimer's disease pathogenesis 6.