Regulation of TRPM8 channel activity

► TRPM8 is a cold- and menthol-activated Ca2+ permeable non-selective cation channel, expressed in sensory neurons. ► TRPM8 is a well established physiological cold sensor. ► The activity of TRPM8 depends on the presence of phosphatidylinositol 4,5-bisphosphate (PIP2). ► Calcium induced activation of phospholipase C and the ensuing depletion of PIP2 mediates desensitization of TRPM8. ► Various other cellular signaling pathways modulate TRPM8 activity.