What do we really know and what do we need to know: some controversies, perspectives, and surprises

TRP channels comprise one of the most rapid growing research topics in ion channel research, in fields related to ion channels including channelopathies and translational medicine. We provide here a critical survey on our current knowledge of TRP channels and highlight some of the still open or controversial questions. This comprises questions related to evolution of TRP channels; biophysics, i.e., permeation; pore properties and gating; modulation; the still-elusive 3D structure; and channel subunits but also their role as general sensory channels and in human diseases. We will conclude that our knowledge on TRP channels is still at the very beginning of an exciting research journey.