Smooth muscle cells as well as non-excitable cells express multiple cationic channels with variable selectivity for Ca2+, K+, Na+. Several of these channels are sensors of Ca2+ store depletion, G-protein-coupled receptor activation, membrane stretch, intracellular pH, oxidative stress, phospholipid signals and other factors. A novel family of such channels is represented by highly conserved heterotetramer homologues of Drosophila TRP (transient receptor potential). Direct evidence exists for roles of TRPC1, TRPC4/5, TRPC6, TRPV, TRPP in store-operated Ca2+- gating in various tissues, including epithelial cell Ca2+ transport, thus controlling renal and intestinal homeostasis of divalent cations. Mice deficient in TRPV5 display phenotypic defects amongst which hypercalciuria and impaired bone mineral density. Polycystin 2 (PC2), encoded by the PKD2 gene, is an epithelial transmembrane protein whose mutation is associated to autosomal dominant polycystic kidney disease (ADPKD). PC2 behaves as a TRP-type Ca2+-permeable nonselective cation channel located on the cilia of tubular epithelial cells. Recent studies indicate that a PC1-PC2 channel complex is an obligatory novel signaling pathway implicated in the transduction of environmental signals into cellular events. TRPrelated ion channels may also play a role in the pathogenesis of arterial hypertension through direct effects on vascular smooth muscle contraction, renal perfusion/hemodynamics, and the total body balance of divalent cations.