The roles of apolipoprotein E (apoE) in regulating plasma lipids and lipoproteins levels have been investigated for over several decades. However, in different tissues/cells, the role of apoE was different, such as that it was a risk factor for cancer, but some reports stated that apoE was a protective factor for renal diseases. At the moment, most of the studies find that apoE not only acts as a ligand for metabolism of lipids, but also plays as a factor to regulate lots of signaling pathways. There was rare review to sum up the signaling pathways for apoE, and there was also rare review to widely review the gene expression of apoE in glomerulus diseases. This review was performed to provide a relatively complete signaling pathways flowchart for apoE to the investigators who were interested in the roles of apoE in the pathogenesis of glomerulus diseases. In the past decades, some studies were also performed to explore the association of apoE gene expression with the risk of glomerulus diseases. However, the role of apoE in the pathogenesis of glomerulus diseases was controversial. Here, the signal transduction pathways of apoE and its role of gene expression in the pathogenesis of glomerulus diseases were reviewed.