Transcription factor which binds the E box motif 5'-CA[TC][AG]TG-3' (PubMed:15470499, PubMed:18356286). Involved in regulating energy expenditure, body mass, voluntary physical activity, mating behavior and reproductive longevity, acting through the hypothalamic-pituitary-gonadal axis (PubMed:15470499, PubMed:12419415, PubMed:9090387, PubMed:17717072, PubMed:23785158, PubMed:15465527). Acts as a transcriptional activator of target genes, including Ndn and Pcsk1 (PubMed:15470499, PubMed:18356286). May act centrally to regulate function of both white and brown adipose tissue (PubMed:20808804, PubMed:19436734). Together with NHLH1, required to maintain migration and survival of cells in the anterior extramural migration stream (aes), which forms the precerebellar nuclei (PubMed:17573818). Also, in concert with Nhlh1, may determine fate of gonadotropin releasing hormone-1 (GnRH-1) neurons (PubMed:15470499). Homodimer. Interacts and may form heterodimers with STAT3. Expressed in developing neurons (PubMed:1633105). Transiently expressed in the cerebellum during postnatal development, exclusively in the premigratory zone of the external granule layer where postmitotic neurons undergo initial stages of neuronal differentiation (PubMed:9011755). Expression is not detected in mature neurons (PubMed:9011755). Expressed in the anterior lobe of the adult pituitary (PubMed:9090387). Expressed in embryos at 10.5-13 days post coitus (dpc), including developing ventral hypothalamus, Rathke's pouch and subventricular layers of the developing diencephalon (PubMed:1633105, PubMed:9090387). Expressed in the vomeronasal organ, olfactory epithelium, and vomeronasal nerve fibers at 14.5 to 16.5 dpc (PubMed:15470499). Expressed in various areas of the developing hypothalamus at 18.5 dpc, including the septal areas, the diagonal band of Broca (DBB), within the organum vasculosum lateralis terminalis (OVLT) region, in the paraventricular nucleus (PVN), in lateral areas of the hypothalamus (LH), in the arcuate nucleus (ARC), and in the dorsomedial hypothalamic nucleus (DMH) (PubMed:15470499). Also expressed in the developing pons from 14.5 dpc onwards, including the pontine and reticulotegmental nuclei (PubMed:17573818). Disruption of the hypothalamic-pituitary axis in both genders, but female pubertal development is influenced by the presence or absence of male mice (PubMed:9090387, PubMed:17717072). Altered female sexual behavior and reproductive longevity, with fewer pregnancies over a shorter period, abnormal estrous cycles and reduced ovulation with aging (PubMed:15465527). Reduction in neuroendocrine gonadotropin releasing hormone-1 (GnRH-1) cell number and altered location of these cells, and morphological and functional abnormalities of the adenohypophysis (PubMed:17717072, PubMed:15470499). Ndn expression almost abolished at the level of the optic chiasma in the hypothalamus (PubMed:15470499). Hypothalamic Pcsk1 expression does not respond to signals of energy availability (PubMed:18356286). Progressive adult-onset obesity, preceded by reduced physical activity (PubMed:9090387, PubMed:12419415). Significant reduction in the innervation and vascularization of white adipose tissue and accumulation of preadipocyte/macrophage-like cells, prior to onset of obesity (PubMed:19436734). Defective torpor response and altered serum leptin levels, body temperature and adipose inflammation (PubMed:20808804). Conditional knockout in GnRH neurons but not in pro-opiomelanocortin (POMC) neurons reduces POMC neuron number and increases visceral fat mass (PubMed:23785158). Double knockout of Nhlh1 and Nhlh2 genes causes neonatal lethality, complete absence of GnRH-1 neurons in the posterior parts of the brain at 18.5 days post coitus (dpc) and aberrant morphology of the remaining GnRH-1 neurons in the anterior parts of the brain (PubMed:15470499). Double knockout of Nhlh1 and Nhlh2 genes causes absence of pontine nuclei, which belong to the precerebellar nuclei and are located either side of the midline of the ventral rhombencephalon (PubMed:17573818). Has been reported to be expressed in Rathke's pouch and the developing pituitary gland (PubMed:9090387). However, a later report found no expression in these tissues and speculated that earlier results may represent cross-hybridization with the very similar Nhlh1 gene (PubMed:15470499).