ABSTRACT Hypoxia-Inducible Factor-1 alpha (HIF-1α) is a critical transcription factor that plays a central role in the cellular response to oxygen levels. HIF-1α is involved in cellular adaptation to hypoxia in eukaryotes and all vertebrates and invertebrates. More than a hundred gene binding sites have been identified on fifteen chromosomes. It plays a critical role in metabolism, angiogenesis, hematopoiesis, proliferation and migration of epithelial cells, bone metabolism, erythropoiesis, immunity, inflammation, cancer, epigenetic regulation, apoptosis and autophagy.