PGP and cancer: Although several E3 ligases have been identified that either recognise P-gp as a substrate [95] or indirectly regulate [98,99,100] P-gp in the context of cancer, only one E3 ligase, namely neural precursor cell-expressed developmentally downregulated protein 4-1 (NEDD4-1), has thus far been investigated with respect to P-gp expression in the brain.