Significance Ion channels are protein pores that allow passive transmembrane ion flow. These pores are opened and closed (gated) by various cellular signals. Typically, the mechanism of gating conformational changes is an equilibrium process, but for some channels, gating is an irreversible cycle, for example, linked to an enzymatic activity. For equilibrium mechanisms, channel activity is readily modulated by energetic stabilization of closed or open states, whereas for cyclic gating, alteration of transition-state stabilities most effectively modulates activity. Transient receptor potential melastatin 2 (TRPM2), a cation channel involved in multiple physiologic and pathophysiologic processes, possesses enzymatic activity, which cleaves its activating ligand. This work addresses, and rules out, a suggested link between that catalysis and pore gating in TRPM2, classifying it among the channels that gate at equilibrium.