HIF1AN is a critical oxygen sensor that hydroxylates hypoxia-inducible factor 1-alpha (HIF-1α) at asparagine-803 in its C-terminal transactivation domain, preventing HIF-1α interaction with coactivators like CBP/p300 under normoxic conditions 1. Beyond HIF-1α regulation, HIF1AN hydroxylates specific asparagine, aspartate, and histidine residues within ankyrin repeat domains of multiple proteins including NOTCH1, ASB4, NFKB1, and others, functioning as a broad post-translational modifier [UniProt annotation supported by 21]. HIF1AN negatively regulates NOTCH1 signaling to promote myogenic differentiation while positively regulating ASB4 to enhance vascular differentiation. Disease relevance spans multiple pathologies: in keloid fibroblasts, reduced HIF1AN expression (via miR-181a-5p and miR-31 upregulation) promotes pathological proliferation and extracellular matrix deposition 34. In spermatogenesis, ASB9-mediated HIF1AN degradation suppresses stem cell proliferation and promotes apoptosis, with dysregulation implicated in non-obstructive azoospermia 5. HIF1AN polymorphisms interact with body fatness to influence breast cancer risk 6, while miR-135b-mediated HIF1AN downregulation reduces proliferation in hormone receptor-positive breast and prostate cancers 7. In osteoblasts, HIF1AN suppression via the SNHG1/miR-497-5p axis enhances osteogenic differentiation, suggesting therapeutic potential for osteoporosis 8. These diverse regulatory roles position HIF1AN as a multifunctional protein linking oxygen sensing, developmental processes, and disease pathogenesis.