Transient receptor potential (TRP) channels are multifunctional signalling molecules
with many roles in sensory perception and cellular physiology. Therefore, it is not
surprising that TRP channels have been implicated in numerous diseases, including
hereditary disorders caused by defects in genes encoding TRP channels (TRP channelopathies).
Most TRP channels are located at the cell surface, which makes them generally accessible
drug targets. Early drug discovery efforts to target TRP channels focused on pain,
but as our knowledge of TRP channels and their role in health and disease has grown,
these efforts have expanded into new clinical indications, ranging from respiratory
disorders through neurological and psychiatric diseases to diabetes and cancer. In
this Review, we discuss recent findings in TRP channel structural biology that can
affect both drug development and clinical indications. We also discuss the clinical
promise of novel TRP channel modulators, aimed at both established and emerging targets.
Last, we address the challenges that these compounds may face in clinical practice,
including the need for carefully targeted approaches to minimize potential side-effects
due to the multifunctional roles of TRP channels.
