Heat shock 70 kDa protein 5 (HSPA5)

Heat shock 70 kDa protein 5 (HSPA5), widely referred to as GRP78 or BiP, is a central molecular chaperone located in the endoplasmic reticulum (ER) lumen (UniProt: P11021). Its fundamental biological role involves assisting in the proper folding and assembly of newly synthesized proteins, preventing their aggregation, and acting as the master regulator of the unfolded protein response (UPR) by sensing ER stress (NCBI Gene: 3309). Under physiological conditions, HSPA5 is vital for maintaining proteostasis and calcium homeostasis; however, it is significantly upregulated in various cancers and viral infections (PubMed: 28241011). In malignant cells, HSPA5 can translocate to the cell surface, where it acts as a receptor promoting survival, metastasis, and chemoresistance, making it a valuable target for selective therapy (PubMed: 20689753). Current therapeutic strategies include small molecule inhibitors like HA15 that block its ATPase activity and monoclonal antibodies such as PAT-SM6 that target surface-bound HSPA5 to induce apoptosis (PubMed: 27151146). While targeting this protein is promising for treating solid tumors and viral pathogens like SARS-CoV-2, potential toxicity to normal secretory tissues remains a critical safety consideration (PubMed: 32709605).

Other names

78 kDa glucose-regulated proteinGRP78Binding-immunoglobulin proteinBiPEndoplasmic reticulum lumenal Ca(2+)-binding protein grp78MIF2

Inhibition of ATPase activity to trigger ER stress-mediated apoptosis, or monoclonal antibody targeting of cell-surface HSPA5 to induce tumor-specific cell death (PubMed: 27151146).