CLU, also known as clusterin or apolipoprotein J (apoJ), is a highly evolutionary conserved glycoprotein. It functions as a molecular chaperone and is involved in a broad range of physiological and pathophysiological functions, exerting a cytoprotective role. It participates in processes like programmed cell death, metastasis, invasion, proliferation, and cell growth, regulating diverse signaling pathways [2,3].

In oral cancer cells, CLU localizes to mitochondria and acts as an adaptor protein. It coordinates with BAX and LC3 to induce mitophagy in response to cisplatin treatment, controlling mitochondrial damage. Inhibition of its related mitophagic flux can lead to ROS-dependent apoptosis. Also, in oral cancer stem cells, CLU promotes mitophagic degradation of MSX2 through an AKT-DNM1L/Drp1 axis, maintaining SOX2-mediated stemness. Knockdown of CLU disturbs mitochondrial metabolism and improves cisplatin sensitivity [1,4].

In conclusion, CLU plays essential roles in maintaining mitochondrial homeostasis, cell survival, and cancer cell stemness. Studies, especially those related to its knockdown in oral cancer models, reveal its significance in cancer biology, suggesting that targeting CLU could potentially be a therapeutic strategy against oral cancer.