HIF1A encodes hypoxia-inducible factor 1 alpha, an oxygen-regulated transcriptional activator that functions as a master regulator of cellular hypoxic responses 1. Under normoxic conditions, HIF1A is subjected to oxygen-dependent ubiquitination and proteasomal degradation mediated by the von Hippel-Lindau protein; hypoxia stabilizes HIF1A, enabling its interaction with coactivators and transcriptional activation 1. HIF1A regulates genes crucial to cancer biology, including those governing angiogenesis, cell survival, glucose metabolism, and invasion 2. Beyond hypoxic responses, HIF1A plays a pathogenic role in viral infections—upon SARS-CoV-2 infection, HIF1A induces glycolysis in monocytes, promotes ACE2 and pro-inflammatory cytokine expression (IL1B, TNF, IL6), and facilitates viral replication 3. In tumor immunology, HIF1A exhibits a complex dual role: while its inhibition in natural killer cells unleashes anti-tumor immunity via NF-κB activation 4, elevated HIF1A expression in tumors correlates with increased immune infiltration, PD-L1 expression, and aggressive phenotypes associated with worse survival 5. Additionally, HIF1A stabilization through deubiquitination by USP51 promotes colorectal cancer stemness and chemoresistance via a positive feedback loop 6. HIF1A variants show associations with multiple cancer types and disease susceptibilities 7, establishing it as both a critical physiological regulator and a promising therapeutic target.