The invention relates to methods useful in identifying molecules that bind TRPM5, which modulate TRPM5 ion channel activity, and/or which alter expression of TRPM5 within cells. The TRPM5 channels as described herein contain TRPM5 polypeptides, which are in turn encoded by TRPM5 nucleic acids. The ion channels described herein are preferably formed in HEK-293 cells from one or more novel TRPM5 polypeptides, which exhibit one or more of the unique TRPM5 properties described herein.