Clusterin (CLU) is a multifunctional glycoprotein with diverse roles in neuroprotection and cellular homeostasis. Primary function: CLU acts as an anti-inflammatory and cytoprotective agent, existing in nuclear, cytoplasmic, and secreted forms 1. In the brain, CLU reduces neuroinflammatory gene expression by binding to brain endothelial cells 2 and modulates astrocyte reactivity to maintain synaptic integrity 3. Mechanism: CLU interacts with complement cascade components and TLR4 signaling to suppress NF-κB-dependent inflammation 34. In mitochondrial contexts, CLU functions as an adaptor protein coordinating BAX and LC3 to facilitate mitophagy and maintain mitochondrial homeostasis 5. CLU also facilitates amyloid-beta clearance through TREM2-mediated microglial uptake of lipoprotein complexes 6. Disease relevance: CLU is implicated in Alzheimer's disease pathogenesis; reduced CLU levels associate with heightened inflammatory profiles and cognitive decline 3, while CLU upregulation correlates with cognitive maintenance 3. CLU expression is altered downstream of SORL1, a major AD risk gene 7. Clinical significance: Exercise increases plasma CLU levels, linking it to cognitive benefits and reduced neuroinflammation 2. CLU inhibition sensitizes cancer cells to chemotherapy 5, suggesting therapeutic potential.