The transient receptor potential, subfamily C (TRPC) channels are ubiquitously expressed among cell types and mediate signals in response to phospholipase C (PLC)-coupled receptors[1]. Among the TRPs, the 6 members of the human TRPC subfamily are unique in that they are not only responsible for agonist-activated nonselective cation currents, but they also participate in the so-called slow sustained mode of Ca2+ signaling, which requires sustained elevations of intracellular Ca2+ ([Ca2+]i)[2]. For all organisms, detection and adaptation to cold temperature is crucial to survival. Cold sensing in the innocuous range of cold (>10-15 °C) in the mammalian peripheral nervous system is thought to rely primarily on transient receptor potential (TRP) ion channels, most notably the menthol receptor, TRPM8. The TRP cation channel, subfamily C member 5 (TRPC5), is found to be highly sensitive to cold in the temperature range 37–25 °C, and is thus hypothesized to play a role in sensing cold[3]. Additionally, the channel may have an important role in the pathogenesis of hypertension[4].