Neural epidermal growth factor-like protein 2 (NELL2)

Neural epidermal growth factor-like protein 2 (NELL2) is a secreted, multimodular glycoprotein highly expressed in neural tissue and involved in critical aspects of neuronal development, such as polarization, axon elongation, branching, and synaptic remodeling[1][2][3]. The protein contains von Willebrand factor C domains, a thrombospondin-1-like domain, and multiple EGF-like repeats, and it acts both extracellularly—by binding to the Roundabout (Robo) family of axon guidance receptors—and intracellularly by modulating PKC and ERK signaling pathways[1][4]. NELL2 expression is necessary for proper neuronal differentiation and axon morphogenesis, and alterations in its expression or activity have been linked to cancer, neurodevelopmental disorders, and may serve as diagnostic or prognostic biomarkers in select neurological conditions[3][2]. No drugs currently target NELL2 directly, and its function as a ligand, not a classical receptor, means therapeutic targeting is still experimental.

Other names

NEL-like protein 2NEL (original chick homolog)Neural EGFL-like 2NELL2

Binds as a ligand to Robo2 and Robo3 receptor proteins (Roundabout family) Modulates ERK and PKC signaling pathways intra- and extracellularly