GRPEL2 is a mitochondrial nucleotide exchange factor essential for regulating mitochondrial protein import and quality control. As a component of the PAM complex, GRPEL2 facilitates the translocation of transit peptide-containing proteins into the mitochondrial matrix by modulating mtHSP70's nucleotide-binding cycle 1. GRPEL2 associates with mtHSP70 as a hetero-oligomeric subcomplex, helping fine-tune chaperone activity and regulate crucial functions including preprotein import and Fe-S cluster biogenesis 1. However, GRPEL2 exhibits preferential binding to ADP-bound mtHSP70 compared to GRPEL1 and lacks the capacity to enhance mtHSP70 ATPase activity 2. GRPEL2 functions as a stress-regulated redox sensor, with its Cys87 residue serving as a thiol switch that promotes dimerization under oxidative stress conditions 3. This redox regulation appears to enhance mitochondrial proteostasis during cellular stress 3. Clinically, GRPEL2 is upregulated in multiple cancers including glioblastoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma, correlating with poor prognosis 4567. In glioblastoma, GRPEL2 knockdown inhibits proliferation and induces cell cycle arrest through reduced oxidative respiration 4. In esophageal cancer, GRPEL2 depletion triggers apoptosis via JNK pathway activation 7. Additionally, GRPEL2 hypomethylation has been associated with vinyl chloride-induced DNA damage 8.