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Clusterin is a multifunctional glycoprotein found in various tissues and body fluids. It is involved in a number of physiological and pathological processes such as apoptosis, protein homeostasis, cancer and Alzheimer’s disease. Although clusterin expression in myeloid cells has been reported, its influence in dendritic cell (DC) function has yet to be analyzed. Therefore, the purpose of our experiment was to determine the role of clusterin in DC survival. First, we analyzed whether activation of human monocyte‐derived DCs resulted in clusterin production. This was done by culturing cells for 48 hours with or without LPS (10 ng/ml). Clusterin was analyzed by western blot and quantified by ELISA. A basal expression level of clusterin was observed in unstimulated DCs, while an increase in production was noted upon activation of these cells by LPS: clusterin concentration in cell supernatant was 0.04 ± 0.1 vs 7.47 ± 2.14 ng/ml (control vs LPS, mean ± ES, n=5, p<0.01 vs unstimulated cells). In order to understand the dynamics of production after activation, we constructed a production curve measuring the level of clusterin post stimulation over a period of four days. A peak in the production of intracellular and secreted clusterin was noted 48 – 72 hours post stimulus. Finally, a knockdown (KD) strategy using a lentiviral gene silencing protocol that delivered a clusterin and scramble (SCR) shRNA was used to determine the role of clusterin in DC function. Two lentiviral combinations were used due to their ability to knockdown >85% of clusterin expression, as evaluated by western blot (in HeLa cells) and rtPCR (DCs). Puromycin was used as a selection drug and a Ficoll gradient was used to separate live and dead cells. We found that silencing clusterin expression (CLU‐KD) resulted in a massive death of DCs upon stimulation with LPS, as evaluated by anexin‐V/propidium straining: 63.7 ± 11.8, 19.7 ± 4.9, and 25.2 ± 6.5% of dead cells, for LPS‐stimulated CLU‐KD DCs, LPS‐stimulated scramble DCs, and unstimulated DCs, respectively (mean ± ES, n=4, p<0.01 CLU‐KD vs scramble or unstimulated DCs). These observations uncover a novel function of clusterin as a key player in the control of the adaptive immune response. Support or Funding Information Roy Mendoza was supported by the grant LA Basin Minority Health and Health Disparities Research Training Program (MHRT) T37MD001368 from the National Institute on Minority Health and Health Disparities, National Institute of Health.