HSPH1 (heat shock protein family H member 1) functions primarily as a nucleotide exchange factor (NEF) for HSP70 chaperones, promoting ADP release and enhancing protein folding activities 1. The protein prevents aggregation of denatured proteins under cellular stress conditions and belongs to the HSP110 family 1. Mechanistically, HSPH1 cooperates with DNAJB1 to facilitate HSP70 loading for amyloid fibril disaggregation, contributing to protein quality control beyond classical chaperone functions 2. The protein physically interacts with key oncoproteins including c-Myc and Bcl-6, promoting their stabilization in aggressive B-cell lymphomas 3. HSPH1 also interacts with SLC7A11 to increase protein stability and regulate ferroptosis resistance 4. Disease relevance is significant, as HSPH1 overexpression correlates with poor prognosis across multiple cancers including hepatocellular carcinoma, gastric cancer, and B-cell lymphomas 143. Clinically, HSPH1 serves as a potential prognostic biomarker and therapeutic target, with its expression detectable in extracellular vesicles and associated with neonatal sepsis prediction 56. The protein's dual role in protein homeostasis and oncogenesis makes it a promising candidate for cancer therapy development.