GRP78: A Multifaceted Role in Cancer Progression and Infectious Disease Transmission

The 78-kDa glucose-regulated protein GRP78, also known as HSPA5 or BiP, is a heat shock protein 70 family member that promotes functions of the endoplasmic reticulum, such as protein folding and assembly, prevention of aggregation of misfolded proteins, translocation of secreted proteins, and initiation of the unfolded protein response. GRP78 may also be a cancer marker. When small extracellular vesicles containing GRP78 are released from cancer cells, recipient cells exhibit enhanced malignant progression and angiogenesis. Further, GRP78 has a critical role in infectious diseases. For example, GRP78 is thought to be involved in the entry mechanism of SARS-CoV-2, the causative agent of COVID-19, into host cells through the angiotensin-converting enzyme 2. Thus, GRP78 has multifaceted roles. The development of GRP78 inhibitors is now being investigated in the cancer field. Whether these inhibitors will also be effective against infectious diseases, however, remains unclear. Here, we review the functions of GRP78 in cancer and infectious diseases, thereby highlighting the need for further research and development.