indicating they may simply have diversified greatly from other closely related proteins. Insects have a third sub-family of TRPP, called brividos, which participate in cold sensing. TRPS TRPS, S for Soromelastatin, was named as it forms a sister group to TRPM. TRPS is broadly present in animals, but notably absent in vertebrates and insects (among others). TRPS has not yet been well described functionally, though it is known that the C. elegans TRPS, known as CED-11, is a calcium channel which participates in apoptosis. TRPV TRPV, V for "vanilloid", was originally discovered in Caenorhabditis elegans, and is named for the vanilloid chemicals that activate some of these channels. These channels have been made famous for their association with molecules such as capsaicin (a TRPV1 agonist). In addition to the 6 known vertebrate paralogues, 2 major clades are known outside of the deterostomes: nanchung and Iav. Mechanistic studies of these latter clades have been largely restricted to Drosophila, but phylogenetic analyses has placed a number of other genes from Placozoa, Annelida, Cnidaria, Mollusca, and other arthropods within them. TRPV channels have also been described in protists. TRPVL TRPVL has been proposed to be a sister clade to TRPV, and is limited to the cnidarians Nematostella vectensis and Hydra magnipapillata, and the annelid Capitella teleta. Little is known concerning these channels. TRPY TRPY, Y for "yeast", is highly localized to the yeast vacuole, which is the functional equivalent of a lysosome in a mammalian cell, and acts as a mechanosensor for vacuolar osmotic pressure. Patch clamp techniques and hyperosmotic stimulation have illustrated that TRPY plays a role in intracellular calcium release. Phylogenetic analysis has shown that TRPY1 does not form a part with the other metazoan TRP groups one and two, and is suggested to have evolved after the divergence of metazoans and fungi. Others have indicated that TRPY are more closely related to TRPP. Structure TRP channels are composed of 6 membrane-spanning helices (S1-S6) with intracellular N- and C-termini. Mammalian TRP channels are activated and regulated by a wide variety of stimuli including many post-transcriptional mechanisms like phosphorylation, G-protein receptor coupling, ligand-gating, and ubiquitination. The receptors are found in almost all cell types and are largely localized in cell and organelle membranes, modulating ion entry. Most TRP channels form homo- or heterotetramers when completely functional. The ion selectivity filter, pore, is formed by the complex combination of p-loops in the tetrameric