HSP90B1 is an ATP-dependent molecular chaperone localized to the endoplasmic reticulum (ER) that facilitates protein folding, trafficking, and receptor signaling. Mechanistically, HSP90B1 promotes proper folding and cell surface localization of key signaling receptors, including LRP6 (a Wnt pathway coreceptor) in conjunction with MESD 1, and Toll-like receptors (TLRs) when associated with CNPY3 2. HSP90B1 also participates in unfolding and translocation of cytosolic leaderless cargo proteins like IL-1 for secretion via the ERGIC 3. Recent evidence reveals that HSP90B1 N-glycosylation is actively regulated by a specialized ER pathway involving CCDC134 and oligosaccharyltransferases; disruption of this pathway impairs WNT and IGF1R signaling and causes osteogenesis imperfecta, demonstrating HSP90B1's critical developmental role 4. HSP90B1 functions within multichaperone condensates that enhance ER folding capacity 5. Clinically, HSP90B1 is highly expressed across multiple cancer types and correlates with poor prognosis, showing negative association with anti-tumor CD8+ T cells and positive correlation with immune checkpoint genes 6. Cancer-derived exosomal HSP90B1 promotes pre-metastatic niche formation by polarizing macrophages toward immunosuppressive M2 phenotypes 7. Additionally, elevated HSP90B1 in multiple myeloma tumor cells associates with CAR-T therapy resistance 8.