HSPA6 is an inducible molecular chaperone belonging to the heat shock protein 70 (Hsp70) family, encoded on human chromosome 1.3 1. It functions as a key component of the protein quality control system through ATP-dependent cycles: in its ATP-bound state, HSPA6 exhibits low substrate affinity, but ATP hydrolysis induces conformational changes that increase affinity for misfolded polypeptides, enabling protein refolding and directing damaged proteins for degradation 2. HSPA6 expression is characteristically low or undetectable under basal conditions but becomes highly stress-inducible through complex promoter regulation involving AP1 sites and heat shock elements 3. Notably, HSPA6 demonstrates context-dependent roles in disease: it exhibits dichotomous effects in cancers, inhibiting tumorigenesis in some cancer types while promoting it in others 1. Recent evidence reveals HSPA6's involvement in multiple pathologies—including regulating spermatogonial stem cell proliferation via the CITED2-EP300 axis 4, promoting osteosarcoma metastasis through AMPK pathway activation 5, and contributing to stress-like phenotypes in immune cells during colorectal neuroendocrine tumor metastasis 6. Additionally, HSPA6 is dysregulated in hepatic ischemia-reperfusion injury following liver transplantation 7. These findings establish HSPA6 as both a therapeutic target and prognostic marker across multiple disease contexts.