There is a rapidly expanding protein family which encompasses a broad repertoire of cation-selective channels serving as a continuous Ca2+ entry pathway into the cell. The transient receptor potential protein (TRP) and its relatives, which were originally thought to be Ca (2+)-permeable cation channels activated upon the stimulation of G-protein coupled and tyrosine kinase receptors, are now becoming promising candidates mediating a variety of cellular responses and functions such as mechano/chemo-transduction, oxidative stress, and cell survival/proliferation. This short paper briefly overviews the current knowledge about these proteins as a new target for drug discovery and development.