ATP-binding cassette (ABC) transporters are a huge family of ATP-dependent
transmembrane proteins whose main function is exporting or importing substances or molecules
through the cell membranes, plasma cell membrane, or inner membranes in organelles.
They fulfill these functions by maintaining cell integrity, metabolism, and homeostasis. They
are expressed in a variety of tissues as they transport numerous essential compounds including
lipids and other signaling molecules. ABC transporters became widely studied since the
discovery of their ability to carry a multitude of xenobiotics, including therapeutic drugs, and
in light of the fact that they represent a hurdle for the treatment of resistant cancers. In contrast,
the role of ABC transporters in neurological diseases like Alzheimer`s and Parkinson`s,
depression, schizophrenia, and epilepsy remains controversial and their mechanism of action
in these pathologies remains elusive, thus hindering the implementation of therapies aimed at
modulating the functions of these transporters. To date, a number of natural and synthetic
compounds are known to act as inhibitors, substrates, and even inducers of these transporters, being able to modulate
their expression and/or function; however, their implication as therapeutic agents is far from reaching wide
clinical utilization. This review highlights the importance of overcoming the challenges posed by ABC transporters
in drug development.