A cDNA encoding a two-pore domain potassium (K2p) channel subunit, AcK2p2, was cloned from the CNS of the marine opisthobranch Aplysia californica. This is the second K2p subunit to be identified in molluscs. Like the K2p subunit cloned previously from Aplysia, AcK2p2 appears to be more closely related to human K2p channels than to any from Drosphila melanogaster or Caenorhabditis elegans. However, the overall identity is much lower (24% with human TALK-1) and phylogenetic analysis indicates that AcK2p2 cannot be grouped into any established mammalian subclass. We analyzed the distribution of this channel by in situ hybridization in whole mount preparations of the CNS. Less than a dozen of the approximately 20,000 neurons in the CNS expressed AcK2p2 at high levels, with the consistently intense labeling seen in a single bilaterally symmetrical pair of pedal neurons. The neuron-specific expression pattern seen for this channel is consistent with data from a variety of organisms that implicate K2p channels as determinants of neuronal phenotype and function.