MAN2B2 (mannosidase alpha class 2B member 2) is a lysosomal enzyme that specifically cleaves terminal alpha 1,6-linked mannose residues from Man3GlcNAc and Man2GlcNAc oligosaccharides during N-glycan degradation, showing minimal activity on larger mannose oligosaccharides 12. The enzyme acts complementarily with lysosomal alpha-mannosidase (MAN2B1) to effect complete glycan degradation within lysosomes 3. MAN2B2 is ubiquitously expressed across tissues 4 and exhibits differential inhibition patterns and metal binding properties compared to related mannosidases 3. Pathogenic variants in MAN2B2 cause congenital disorders of glycosylation type 1EE (MAN2B2-CDG), a rare inherited metabolic disorder characterized by disrupted N-linked glycosylation patterns 56. Clinical manifestations include developmental delay, dysmorphic facial features, immune dysregulation, and gastrointestinal dysfunction 756. MAN2B2 expression is upregulated in Gram-positive bacterial sepsis in preterm neonates, potentially contributing to immunomodulatory responses 8. Understanding MAN2B2 function is critical for comprehending N-glycan metabolism and developing targeted therapies for glycosylation disorders.