METAP2 (methionyl aminopeptidase 2) is a metalloprotease that removes N-terminal methionine residues from nascent proteins, playing a critical role in protein synthesis regulation 1. Beyond its canonical aminopeptidase function, METAP2 protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation and regulates lipid metabolism and energy balance 1. METAP2 serves as a cytoplasmic shuttle protein in targeted protein relocalization mechanisms, facilitating redistribution of disease-associated proteins to alter cellular interactomes 2. In cancer biology, METAP2 is upregulated in ovarian cancer where it stabilizes the RNA-binding protein YTHDF2 by attenuating K48-linked ubiquitination, promoting cancer cell proliferation and migration through altered mRNA decay of tumor suppressors 3. Therapeutically, METAP2 inhibitors including fumagillin, TNP-470, beloranib, and ZGN-1061 show promise across multiple disease contexts 1. Recent evidence demonstrates METAP2 inhibitor BL6 reduces neuroinflammation in microglia and Alzheimer's disease models by suppressing pro-inflammatory cytokines and promoting microglial polarization 4. Additionally, MetAP2 is an essential survival factor in microsporidian parasites and represents a validated antimicrobial drug target 5. These diverse functions position METAP2 as a pleiotropic therapeutic target for metabolic, oncologic, and neurodegenerative diseases.