Myelin and Lymphocyte Protein 2 (MAL2), a lipid raft associated protein that is involved in the basolateral-to-apical transcytotic machinery of polarized epithelial cells, has been found to be highly up-regulated in a variety of human carcinomas including cholangiocarcinomas, renal carcinomas, metaplasias of the stomach, and cancers of the breast, ovary and pancreas. Recent work has also correlated MAL2 up-regulation with poor survival in patients with pancreatic cancer. However, it is still unknown how MAL2 up-regulation relates to tumorigenesis and cancer progression. One of the hallmarks of cancer is the loss of cell polarity; in fact, most human carcinomas derive from polarized epithelial cells and are AASLD Abstracts AASLD Abstracts characterized by the loss of or failure to achieve polarity. This is of particular interest to us because MAL2 is thought to be involved with the establishment and/or maintenance of a polarized phenotype. Therefore, it is important to consider how loss or dysregulation of polarized protein trafficking contributes to malignant transformation. To identify possible mechanisms linking MAL2 up-regulation to malignancy, we overexpressed wild-type MAL2 in hepatoma-derived Clone9 cells that lack endogenous MAL2. Our results showed that MAL2 overexpression induced actin-based protrusions formation with MAL2 localized to their tips.