Islet-2 (insulin gene enhancer protein ISL-2) is a 359 amino acid protein encoded by the human gene ISL2. Islet-2 is a nuclear protein that contains two N-terminal LIM domains, followed by a homeodomain and a serine/ glutamine/threonine-rich C-terminus. Islet-2 is a transcriptional factor that defines subclasses of motor neurons that segregate into columns in the spinal cord and select distinct axon pathways. Islet-1 and Islet-2 are initially ex-pressed by all postmitotic spinal motor neurons prior to diversification of somatic and visceral neuronal fates. Somatic, but not visceral, motor neurons maintain Islet-2 expression at later embryonic stages. An early phase of Islet-2 expression by prospective visceral motor neurons of the sympathetic preganglionic motor column is critical for the emergence of complete visceral motor neuron character. Mutations that reduce or eliminate both Islet-1 and Islet-2 activity will result in pronounced defects in visceral motor neuron generation and eroded somatic motor neuron character.