exacerbated in the brains of patients with age-onset neurodegenerative diseases such as Alzheimer's or Huntington's disease. Cancer Over the last two decades HSP90 has emerged as an intriguing target in the war on cancer. HSP90 interacts and supports numerous proteins that promote oncogenesis, thus distinguishing Hsp90 as a cancer enabler as it is regarded as essential for malignant transformation and progression. Moreover, through their extensive interactomes, both paralogs are associated with each hallmark of cancer. The HSP90AA1 gene however is not altered in a majority of tumors according to The Cancer Genome Atlas (TCGA). Currently bladder cancer is found to have the largest number of alterations followed by pancreatic cancer. This may not come as a surprise since overall Hsp90 expression levels are held at such a high level compared to most all other proteins within the cell., therefore further increasing Hsp90 levels may not provide any benefit to cancer growth. Additionally, whole genome sequencing across all tumor types and cancer cell lines reveals that there are presently 115 different mutations within the HSP90AA1 open reading frame. The effects of these mutations on HSP90A function, however, remain unknown. Remarkably, in a number of tumors the HSP90AA1 gene is homozygously deleted, suggesting that these tumors may have a reduced level of malignancy. This is supported by a comparative genome-wide analysis of 206 gastric cancer patients that reported loss of HSP90AA1 is indeed associated with favorable outcomes after surgery alone. This supports the possibility that the absence of Hsp90A in tumor biopsies may serve as a biomarker for positive clinical outcomes. Biologically, Hsp90A differs from Hsp90B in that Hsp90A is presently understood to function as a secreted extracellular agent in wound healing and inflammation in addition to its intracellular roles. These two processes are often hijacked by cancer allowing for malignant cell motility, metastasis and extravasion. Current research in prostate cancer indicates that extracellular Hsp90A transduces signals that promote the chronic inflammation of cancer-associated fibroblasts. This reprogramming of the extracellular milieu surrounding malignant adenocarcinoma cells is understood to stimulate prostate cancer progression. Extracellular HSP90A induces inflammation through the activation of the NF-κB (RELA) and STAT3 transcription programs that include the pro-inflammatory cytokines IL-6 and IL-8. Coincidentally NF-κB also induces expression Hsp90A., thus providing a model where newly expressed Hsp90A would also be secreted from the stimulated fibroblast thereby creating positive autocrine and paracrine feedback loops resulting in an inflammatory storm at the