Heat shock protein 90 beta family member 1 (HSP90B1)

Heat shock protein 90 beta family member 1 (HSP90B1), also known as endoplasmin, GRP94, or GP96, is a major ATP-dependent molecular chaperone resident in the endoplasmic reticulum of eukaryotic cells. It is essential for the proper folding, stability, and function of a specific set of client proteins, including integrins, Toll-like receptors, and some secreted and membrane proteins, thereby playing a key role in the unfolded protein response (UPR) and cellular protein homeostasis. HSP90B1 is distinct from cytosolic HSP90 isoforms and is vital for both normal development and immune system function, with links to tumor progression and infectious diseases. While several experimental drugs and immunotherapies target HSP90B1, toxicity remains a challenge for selective inhibition. Its expression is associated with several diseases, including cancer, certain immune disorders, and rare skeletal dysplasias.

Other names

EndoplasminGRP94GP96TRA1Heat shock protein 90kDa beta (Grp94), member 1Heat shock protein 90 kDa beta member 1Heat shock protein family C member 4Tumor rejection antigen (gp96) 194 kDa glucose-regulated proteinTumor rejection antigen 1ERp99

ATPase inhibition blocks chaperone function—results in misfolding and degradation of client proteins. Modulation of immune chaperoning affects TLR and integrin function. Vaccine mechanism (vitespen): primes adaptive immune response by presenting tumor antigens bound to HSP90B1.