variants regulating gene expression (eQTL) and its expression associates with an inhibited glucose-regulated secretion of insulin in INS1 cells. Upstream regulators PAK5 expression is positively regulated by Aurora-A and both PAK5 and Aurora-A are co-upregulated in esophageal squamous carcinoma. The levels of PAK5 are regulated by miR-129 in hepatocacinoma cancer cells, and by the binding of the long non-coding RNA Colorectal neoplasia differentially expressed (CRNDE) to miR-186 in glioma cells. Downstream targets PAK5 phosphorylates Pacsin-1 and Synaptojanin-1 and regulates synaptic vesicle trafficking. PAK5-mediated phosphorylation of GATA1 at S161 and S187 contributes to Epithelial-mesenchymal transition. PAK5 phosphorylation of p120-catenin at S288 plays a role in cytoskeleton remodeling. In addition to the cytoplasm, the PAK5 also localizes in mitochondria and phosphorylates BAD at S112. PAK5 inhibits the MARK2/Par1 activity and modulates microtubules dynamics. Clinical significance PAK5 levels are upregulated in osteosarcoma, hepatocellular carcinomas, gastric cancer, glioma, esophageal squamous cell cancer, colon cancer, ovarian cancer, and breast cancer. There are also examples of gain-of-function activating PAK5 mutations in non-small-cell lung cancer lung cancer. PAK5 promotes the cell survival and sensitivity of cancer cells to chemotherapy. Notes References