NELL2 is an approximately 140 kDa secreted glycoprotein that exhibits several actions during nervous system development. NELL2 associates into a homotrimer and contains one Laminin G domain, one vWF-C domain, and six EGF-like domains, followed by one more vWF-C domain (1). Mature mouse NELL2 shares 94% and 97% aa sequence identity with human and rat NELL2, respectively. Alternative splicing generates a cytosolic isoform that associates with PKC beta 1 and can inhibit PKC signaling (2). NELL2 is widely expressed in neurons of the central and peripheral nervous systems, particularly in the hippocampus, hypothalamus, cerebral cortex, and cerebellar cortex (3-5). It is selectively expressed in VGAT1+ or VGAT2+ glutamatergic neurons (4, 6). During development, NELL2 is expressed in select neural crest cells, retinal ganglion cells, and hypaxial muscle precursor cells of the dermomyotome (7). It promotes the differentiation and migration of both motor and sensory neurons (8), enhances neuronal survival (9), and promotes neuronal aggregation by inducing N-Cadherin up-regulation (10). NELL2 supports the release of GnRH from the hypothalamus which is important for the onset of female puberty (5, 6). NELL2 is additionally expressed in renal tubules but is down-regulated in renal cancer (11).