One of the outstanding challenges of biological science is to understand the nature, regulation and physiological importance of the various non-selective, calcium- and sodium-permeable cationic channels contained within blood vessels. One reason why this is important is because of the hypothesis that the channels are central to mechanical- and lipid- sensing or transduction; fundamental, enigmatic and interconnected aspects of vascular biology. Candidates for the molecular basis of the underlying channels are the Transient Receptor Potential proteins (TRPs), which are encoded by 28 genes in mammals and generate extensive additional diversity through heteromultimeric assembly. The heteromultimers, still poorly defined in physiology, redundancies within assemblies and intricate and, again poorly defined, relationships with other proteins in restricted sub-cellular spaces (often dominated by cytoskeleton) are challenges that have emerged and prevented straightforward understanding. In this situation, simple molecular deletion, knock-down and over-expression of single TRPs may often be inadequate as experimental strategies. There are also difficulties in defining the appropriate physical and lipid manipulations to mimic the relevant physiological contexts, which include luminal pressure, disturbed shear stress, physical injury, and directional sensing requirements of cell migration and proliferation as blood vessels form and remodel. Despite such complexities, there are tantalising indications that various TRPs are involved (1-5). That almost all TRP subtypes have been implicated may be a reflection of physiological realities, such as needs for back-up systems and multiple sensors and transducers with varied mechanical and lipid sensitivities. The lecture will review data on TRPs in this biological context and outline emerging hypotheses for how the proteins may contribute.