that human Hsp90B interacts with 7% of all transcription factors, 60% of all kinases and 30% of all E3-ligases. Other studies have shown that Hsp90 interacts with various structural proteins, ribosomal components and metabolic enzymes. Hsp90 has also been found to interact with a large number of viral proteins including those from HIV and EBOLA. This is not to mention the numerous co-chaperones that modulate and direct HSP90 activity. Few studies have focused on discerning the unique protein interactions between Hsp90A and HSP90B. Work done in Xenopus eggs and yeast has shown that Hsp90A and Hsp90B differ in co-chaperone and client interactions. However, little is understood concerning the unique functions delegated to each human paralog. The Picard lab has aggregated all available Hsp90 interaction data into the Hsp90Int.DB website. Gene ontology analysis of both Hsp90A and Hsp90B interactomes indicate that each paralogs is associated with unique biological processes, molecular functions and cellular components. Heat shock protein 90kDa alpha (cytosolic), member A1 has been shown to interact with: AHSA1, AKT1, AR, C-Raf, CDC37, DAP3, EPRS, ERN1, ESR1 FKBP5, GNA12, GUCY1B3, HER2/neu, HSF1, Hop, NOS3, NR3C1, P53, PIM1, PPARA, SMYD3, STK11, TGFBR1, TGFBR2, and TERT. Post-translational modifications Post-translational modifications have a large impact on Hsp90 regulation. Phosphorylation, acetylation, S-nitrosylation, oxidation and ubiquitination are ways in which Hsp90 is modified in order to modulate its many functions. A summary of these sites can be found at PhosphoSitePlus. Many of these sites are conserved between Hsp90A and Hsp90B. However, there are a few distinctions between the two that allow for specific functions to be performed by Hsp90A. Phosphorylation of Hsp90 has been shown to have affect its binding to clients, co-chaperones and nucleotide. Specific phosphorylation of Hsp90A residues have been shown to occur. These unique phosphorylation sites signal Hsp90A for functions such as secretion, allow it to locate to regions of DNA damage and interact with specific co-chaperones. Hyperacetylation also occurs with Hsp90A which leading to its secretion and increased cancer invasiveness. Clinical significance Expression of Hsp90A also correlates with disease prognosis. Increased levels of Hsp90A are found in leukemia, breast and pancreatic cancers as well as in patients with chronic obstructive pulmonary disease (COPD). In human T-cells, HSP90AA1 expression is increased by the cytokines IL-2, IL-4 and IL-13. HSP90, alongside other conserved chaperones and co-chaperones that interact to safeguard proteostasis, is repressed in aging human brains. This repression was found to be further