Robert Klipp (left), Megan Cullinan (center), and John Bankston (right) present new details of how the integral monotopic membrane protein STOM inhibits the acid-sensing ion channel ASIC3. The researchers find that STOM interacts with the distal C-terminus of ASIC3 and suppresses the channel’s activity through an interaction with its first transmembrane domain. This interaction may stabilize ASIC3 in its desensitized state because STOM-dependent regulation is abolished by a point mutation that prevents channel desensitization.