HSP90AA1 encodes heat shock protein 90α (Hsp90α), the stress-inducible isoform of the molecular chaperone Hsp90 1. Unlike the constitutively expressed Hsp90β isoform, Hsp90α is regulated through specific transcription factor interactions and unique post-translational modifications 1. HSP90AA1 functions as a critical regulator of cellular stress responses and autophagy. In osteosarcoma, HSP90AA1 promotes chemoresistance by inducing autophagy via the PI3K/Akt/mTOR pathway while simultaneously inhibiting apoptosis through the JNK/P38 pathway 2. Chemotherapy agents including doxorubicin, cisplatin, and methotrexate induce HSP90AA1 upregulation, and suppression of HSP90AA1 restores chemotherapy sensitivity both in vitro and in vivo 2. In neurodegenerative contexts, HSP90AA1 is upregulated in activated microglia in Parkinson's disease patients, associated with pro-inflammatory trajectories characterized by elevated IL1B and GPNMB 3. HSP90AA1 is also identified as a hub target in toxicological networks linked to diabetic microvascular diseases, including diabetic kidney disease 4, and participates in cancer signaling pathways affected by environmental pollutants 5. These findings establish HSP90AA1 as a therapeutic target for improving cancer treatment outcomes and potentially addressing neuroinflammatory diseases.