Heat shock protein family A (Hsp70) member 5 (HSPA5)

Heat shock protein family A (Hsp70) member 5, also known as HSPA5, BiP, or GRP78, is a master chaperone protein predominantly localized to the endoplasmic reticulum (ER) where it facilitates proper protein folding and is essential for quality control of newly synthesized proteins[1][2][3][5][7]. Upon ER stress, HSPA5 can translocate to the cell surface, nucleus, or mitochondria, where it participates in a wide range of cellular processes, including regulation of apoptosis, transcription, proliferation, and immune responses[1][3][5]. HSPA5 is overexpressed in many cancers and other diseases, contributing to cell survival, tumor progression, and drug resistance; it also serves as a host factor in infectious diseases such as COVID-19, making it an important therapeutic target[1][4][5]. Due to its central role in maintaining proteostasis and adapting to cellular stress, targeting HSPA5 can have broad therapeutic effects but also introduces safety challenges due to its critical functions in normal and diseased cells.

Other names

BiPBinding immunoglobulin proteinGRP78Glucose-regulated protein 78Immunoglobulin heavy chain binding protein

Inhibition of chaperone activity (to disrupt protein folding in cancer or viral infections); Promotion of apoptosis or sensitization to apoptosis (anticancer); Modulation of immune function (anti-inflammatory and immunomodulatory effects); Inhibition of viral entry or replication (by blocking cell surface-associated HSPA5)