HSP90AA1

HSP90AA1 encodes Heat Shock Protein 90 Alpha Family Class A Member 1, commonly known as HSP90α, HSP90A, or HSPC1. As a core cytosolic molecular chaperone, it mediates the folding, maturation, and stabilization of over 200 client proteins—including oncogenic kinases (EGFR, HER2), transcription factors (p53, HIF-1α), and signaling adaptors—via an ATP-dependent conformational cycle. It regulates key pathways like PI3K/Akt, MAPK/ERK, and NF-κB, governing cell proliferation, survival, and stress response.
Dysregulation of HSP90AA1 links to multiple diseases: overexpression in breast, lung, and prostate cancers sustains oncoprotein function to drive tumorigenesis; in neurodegenerative disorders like Alzheimer’s, it may exacerbate amyloid-β aggregation. Drug development includes HSP90 inhibitors (geldanamycin derivatives 17-AAG, alvespimycin) tested in cancer trials, but toxicity limits use. Newer isoform-selective inhibitors target HSP90α to improve efficacy and reduce off-target effects, with promising preclinical data for cancer therapy.