The calcium-activated cation channel TRPM4 (transient receptor potential melastatin 4) is ubiquitously expressed. TRPM4 is involved in many calcium-dependent cellular processes, such as control of excitable cell activity, insulin secretion or mast cells degranulation. Recently, it has been found to be overexpressed in prostate cancer cells and contribute to prostate cancer cell proliferation, migration, and invasion. Several genetic variants in the human gene encoding TRPM4 are linked to cardiac conduction disorders leading to arrhythmias in patients. The focus of the project is on cardiac arrhythmias and prostate cancer. Using a combination of virtual screening and several rounds of synthetic optimization we have developed the first potent specific inhibitors of TRPM4. These compounds are currently used in our studies but also developed further into research tools to address specific unresolved questions regarding TRPM4 (patho)physiology. Different experimental models such as in vivo mouse models and human cancer stem cells are investigated with a variety of techniques including biochemical and electrophysiological approaches, and cellular assays. We are exploring if small molecule TRPM4 modulators have therapeutic potential in cardiac dysfunctions and how they might affect prostate cancer cells.