Recent discoveries have revealed that the IMS protein Skd3 is crucial for the disaggregation activities essential for human health.44 In cancer cells, elevated oxidative stress leads to H2O2 accumulation in the IMS, promoting tumor growth.45 Multiple IMS proteins are aberrantly expressed, with 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) promoting mitochondrial energy metabolism in pancreatic cancer and SLP-2 regulating the ROS and extracellular signal-regulated kinase (ERK) pathways in papillary thyroid cancer.46 Here, HPDL is linked to cancer.