NELL2 (neural EGFL like 2) is a secreted glycoprotein containing six EGF-like repeats that functions as a signaling molecule with diverse biological roles 1. NELL2 is predominantly expressed in brain tissue and neuronal cell lineages, with cytoplasmic protein localization observed in neurons 2. The protein mediates autocrine signaling through the Robo3 receptor, activating pathways that regulate cell proliferation and differentiation 3. Mechanistically, NELL2 signaling inhibits cdc42, which leads to upregulation of BAF chr12 remodeling complexes and enhanced transcriptional output 3. In bone biology, NELL2 promotes osteoblast differentiation while inhibiting adipocyte differentiation through fibronectin 1/integrin-mediated FAK/AKT signaling 4. NELL2 exhibits tumor suppressor properties in multiple cancer types, being downregulated through promoter hypermethylation in renal cell carcinoma where it inhibits cell migration and adhesion 5. In hepatocellular carcinoma, NELL2 suppresses epithelial-mesenchymal transition and induces ferroptosis via the Notch signaling pathway 6. Conversely, in Ewing sarcoma, NELL2 functions as an oncogenic dependency, promoting cell growth through BAF complex regulation with the cofactor C4orf48/NICOL 37.