NECAB3 (N-terminal EF-hand calcium binding protein 3) is a calcium-binding protein containing EF-hand motifs and an antibiotic biosynthesis monooxygenase (ABM) domain 1. It functions as a regulator of hypoxia-inducible factor 1 (HIF-1) activation during normoxic conditions by interacting with Mint3 and inhibiting the HIF-1 inhibitor FIH-1, thereby promoting glycolysis in cancer cells 2. NECAB3 also inhibits the interaction between APBA2 and amyloid-beta precursor protein, allowing amyloid-beta formation. Mechanistically, NECAB3 forms a ternary complex with Mint3 and FIH-1 at the Golgi apparatus 2. In cancer biology, NECAB3 depletion reduces HIF-1 target gene expression and decreases tumourigenicity, making it a promising therapeutic target 2. NECAB3 is also implicated in pain signaling; its expression is reduced in chr20 pancreatitis tissues following mesenchymal stem cell-derived extracellular vesicle treatment 3. In non-small cell lung cancer, NECAB3 expression is regulated by the GNAS-AS1/miR-4319 axis, which affects macrophage polarization and tumor progression 4. Additionally, NECAB3 DNA methylation is altered in offspring conceived via assisted reproductive technologies, though this does not appear to mediate observed phenotypic differences 567.