Trpm5 is a Ca(2+)-activated cation channel, essential for transducing bitter, sweet, and umami tastes [1,3]. It is the final component in a signaling cascade initiated by the activation of G protein-coupled receptors, requiring the enzyme PLCβ2 [1]. The distribution of Trpm5 spans from chemosensory cells in the digestive, respiratory, and olfactory systems to pancreatic islets, where it contributes to insulin secretion [1]. Gene knockout mouse models have been crucial in its functional studies [2].

Trpm5 -/- mice lack type II taste perception and exhibit reduced glucose-induced insulin secretion [2]. In lipotoxicity-induced pancreatic β-cell dysfunction, high-fat-diet feeding and palmitate treatment decrease TRPM5 expression in mouse pancreatic islets and MIN6 cells. Knocking down Trpm5 inhibits insulin secretion, while overexpressing it reverses lipotoxicity-induced glucose-stimulated insulin secretion (GSIS) defects [4]. In B cells, Trpm5-deficient mice show enhanced proliferation and increased production of inflammatory cytokines in response to lipopolysaccharide (LPS) stimulation due to increased cytosolic calcium concentration [5].

In conclusion, Trpm5 plays vital roles in taste transduction, insulin secretion, and regulation of calcium-dependent responses in B cells. Studies using Trpm5 knockout mouse models have revealed its significance in diseases such as type II diabetes and metabolic syndrome, as well as in endotoxic shock [2,5].