The biological function of Clusterin has been puzzling researchers for a long time since its first discovery and characterization in the early 80's. CLU plays important roles nearly in all most important biological phenomena including cell proliferation and apoptosis, as well as in many diseases including cancer. Now we know that the CLU gene encodes at least three protein forms with different sub-cellular localization and diverse biological functions. The molecular mechanism of production of these protein isoforms remains unclear. Recent data show that many of the previous hypotheses based on preliminary observations are no longer true. For instance, while alternative splicing of CLU mRNA has never been confirmed, the complex transcriptional regulation of CLU gene is now recognized to produce two distinct transcripts resulting from two independent transcriptional start sites. CLU expression was found deregulated in many type of tumours, including prostate cancer. Considering that prostate cancer is one of the major threats in veterans' life, as well as one of the main causes of cancer related death in western countries, we will also specifically address whether targeting CLU might pave the way for a novel therapeutic intervention against prostate cancer.