the expression of p-gp is also regulated by post-translational events, such as post-transcriptional modification, degradation, and intracellular trafficking of p-gp. pim-1 protects p-gp from ubiquitination and the following degradation in the proteasome. small gtpases rab5 down-regulates the endocytotic trafficking of p-gp and thus increases the functional p-gp level on the cell membrane; while small gtpases rab4 work in an opposite way: rab4 down-regulates the exocytotic trafficking of p-gp from intracellular compartments to the cell membrane, and therefore decreases the functional p-gp level on the cell membrane.