In this study, we used unbiased, quantitative proteomics to identify proteins in the mouse hypothalamus whose abundances are altered by loss of Magel2. This analysis revealed that the secretory granule (SG) abundance and neuropeptide production pathway are dramatically impaired following the loss of Magel2. Previous studies observed hormonal imbalance in PWS patients and Magel2 paternal truncation (Magel2pΔ/m+) mice (1, 4, 11, 27–30). This evidence concerns the gene MAGEL2 and Prader-Willi syndrome.