Following the successful completion of the human genome and the ongoing effort in human proteome, we believe the next wave of activity will be focused on the traffickome —the localization and transportation of all cellular proteins.To this end , we have embarked on a large scale screening for intracellular mediators for the trafficking of cell surface molecules such as MT1-MMP and EGFR.The strategy involves the cloning of more than 500 likely effectors in expression vectors and the construction of their corresponding siRNA vectors .These potential regulators have been screened for their ability to perturb the trafficking patterns ofMT1-MMP in MDCK and PC3 cells.The pos itive candidates are currently being evaluated by co-IP experiments to see if they interact directly with the previously identified adaptor proteins including dynamin, clathrin , components of the AP2 complex , and the PDZ containingMints.The long term goal is to construct a regulatory circuit that regulate the trafficking of MT-MMPs and identify potential targets upstream of MT-MMPs for drug development.