Neuronal growth regulator 1 (NEGR1), also known as neurotractin or Kilon, is a member of the immunoglobulin superfamily’s IgLON subgroup. Structurally, IgLON proteins share three Ig-like C2-type domains and are anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor^1,2. These proteins are implicated in neural development, supporting cellular interactions, neurite outgrowth, and synaptic formation^3,4.

NEGR1 is predominantly expressed in brain tissue, especially in the cerebral cortex, hippocampus, and hypothalamus. At the cellular level, it localizes to neuronal cell membranes where it regulates neurite extension and synapse stabilization^1,5. NEGR1 activity is regulated through interaction with signaling molecules such as leukemia inhibitory factor receptor (LIFR), which affects downstream factors like lipocalin-2 (Lcn2) that are vital for neurogenesis and affective behaviors³.

Functionally, NEGR1 modulates cell adhesion and neurite growth, processes essential for the proper development of neural circuits. It plays roles in both physiological and pathological states; for example, it is linked to hippocampal neurogenesis and synaptic plasticity, influencing behaviors related to anxiety and depression^3,5. Dysfunctions in NEGR1 are associated with obesity, learning difficulties, psychiatric disorders, and mood dysregulation. Knockout studies in mice reveal that the loss of NEGR1 leads to reduced body mass, anxiety-like behaviors, and impaired neurogenesis^2,4.