94千达分子伴侣葡萄糖调节蛋白94（Grp94）由于其直接与内质网（ER）应激和疾病的关联而在过去的十年中引起了人们的兴趣。Grp94属于Hsp90分子伴侣家族，是ER稳态的主要调节因子，因为它能够折叠和稳定蛋白质/受体，并为被误折叠的蛋白质提供伴侣作用以进行降解。多项研究表明，Grp94敲低或抑制会导致客户蛋白底物的降解，进而破坏疾病依赖的信号通路。因此，小分子抑制剂Grp94已成为治疗各种疾病的有前途的治疗途径。具体而言，对于癌症、青光眼、免疫介导炎症和病毒感染，Grp94被证明是一个有前途的靶点。此外，Grp94-肽复合物已有效地作为针对各种疾病状态的疫苗佐剂被利用。这项工作强调了Grp94生物学的重要性以及针对多种疾病状态的分子伴侣的治疗方法的发展。 © 2022 Wiley Periodicals LLC。

The 94 kDa molecular chaperone, glucose-regulated protein 94 (Grp94), has garnered interest during the last decade due to its direct association with endoplasmic reticulum (ER) stress and disease. Grp94 belongs to the Hsp90 family of molecular chaperones and is a master regulator of ER homeostasis due to its ability to fold and stabilize proteins/receptors, and to chaperone misfolded proteins for degradation. Multiple studies have demonstrated that Grp94 knockdown or inhibition leads to the degradation of client protein substrates, which leads to disruption of disease-dependent signaling pathways. As a result, small molecule inhibitors of Grp94 have become a promising therapeutic approach to target a variety of disease states. Specifically, Grp94 has proven to be a promising target for cancer, glaucoma, immune-mediated inflammation, and viral infection. Moreover, Grp94-peptide complexes have been utilized effectively as adjuvants for vaccines against a variety of disease states. This work highlights the significance of Grp94 biology and the development of therapeutics that target this molecular chaperone in multiple disease states.© 2022 Wiley Periodicals LLC.