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Multidrug resistance mediated by the drug-efflux protein P-glycoprotein (P-gp) is one mechanism that tumor cells use to escape death induced by chemotherapeutic drugs. Although it is irrefutable that P-gp can efflux xenobiotics out of cells, biological regulatory functions for P-gp in multicellular organisms have yet to be established firmly. Recent observations have challenged the notion that P-gp has evolved merely to efflux xenotoxins out of healthy cells and raised the possibility that P-gp and related transporter molecules might play a fundamental role in regulating cell differentiation, proliferation and survival.