The change of locomotion activity in response to external cues is a considerable achievement of animals and is required for escape responses, foraging, and other complex behaviors. Little is known about the molecular regulators of such an adaptive locomotion. The conserved eukaryotic two-pore domain potassium (K 2 P) channels have been recognized as regulatory K + channels that modify the membrane potential of cells, thereby affecting, e.g., rhythmic muscle activity. By using the Caenorhabditis elegans system combined with cell-type-specific approaches and locomotion in-depth analyses, here, we found that the loss of K 2 P channel TWK-7 increases the locomotor activity of worms during swimming and crawling in a coordinated mode. Moreover, loss of TWK-7 function results in a hyperactive state that (although less pronounced) resembles the fast, persistent, and directed forward locomotion behavior of stimulated C. elegans. TWK-7 is expressed in several head neurons as well as in cholinergic excitatory and GABAergic inhibitory motor neurons. Remarkably, the abundance of TWK-7 in excitatory B-type and inhibitory D-type motor neurons affected five central aspects of adaptive locomotion behavior: velocity/frequency, wavelength/amplitude, direction, duration, and straightness. Hence, we suggest that TWK-7 activity might represent a means to modulate a complex locomotion behavior at the level of certain types of motor neurons.L OCOMOTION is a fundamental aspect of life, because it is required for escape responses, foraging, and other behaviors. In both invertebrates and vertebrates, rhythmic and patterned locomotion is usually controlled by specific motor circuits with autonomous rhythmic activities called central pattern generators (Marder and Calabrese 1996). The overall output of the motor network depends on the interplay of premotor interneurons, motor neurons, muscle cells, and the intrinsic membrane properties of the involved cells. For example, in insects, motor activity appears to increase during walking by tonic depolarization of interneurons and/or motor neurons (Ludwar et al. 2005). In response to environmental cues, animals often adjust their locomotion activity, which, in principle, can be regulated at the level of central pattern generators, interneurons, motor neurons, or muscle cells. Two-pore domain potassium (K 2 P) channels are evolutionarily conserved eukaryotic membrane proteins (Enyedi and Czirjak 2010). They contain two pore domains per subunit and function as dimers building one conductance pore. K 2 P channels operate as regulatory K + channels to stabilize the negative membrane potential and to counterbalance membrane depolarization. Closure of their potassium pore usually induces membrane depolarization and facilitates the excitability of cells. K 2 P channels are specifically regulated by a variety of factors, including temperature, pH, membrane stretch, fatty acids, and signaling-pathway-dependent phosphorylation. The physiological function of most K 2 P channels remains to be elucid...