This review deals with recent advances in studies on P-glycoprotein (P-gp) and 
its expression regulators, focusing especially on our own research. Firstly, we 
describe findings demonstrating that the distribution of P-gp along the small 
intestine is heterogeneous, which explains why orally administered P-gp 
substrate drugs often show bimodal changes of plasma concentration. Secondly, we 
discuss the post-translational regulation of P-gp localization and function by 
the scaffold proteins ezrin, radixin and moesin (ERM proteins), together with 
recent reports indicating that tissue-specific differences in regulation by ERM 
proteins in normal tissues might be retained in corresponding cancerous tissues. 
Thirdly, we review evidence that P-gp activity is enhanced in the process of 
epithelial-to-mesenchymal transition (EMT), which is associated with cancer 
progression, without any increase in expression of P-gp mRNA. Finally, we 
describe two examples in which P-gp critically influences the brain distribution 
of drugs, i.e., oseltamivir, where low levels of P-gp associated with early 
development allow oseltamivir to enter the brain, potentially resulting in 
neuropsychiatric side effects in children, and cilnidipine, where impairment of 
P-gp function in ischemia allows cilnidipine to enter the ischemic brain, where 
it exerts a neuroprotective action.