Alpha-mannosidase 2C1

Alpha-mannosidase 2C1 (MAN2C1) is a cytoplasmic glycosidase that cleaves alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues from free oligosaccharides generated during N-glycoprotein degradation (UniProt: Q9NTJ4). The enzyme functions in cellular protein quality control pathways involving the breakdown of misfolded glycoproteins.

MAN2C1 is associated with congenital disorder of deglycosylation 2 (CDDG2), a rare autosomal recessive condition characterized by intellectual disability, craniofacial anomalies, and central nervous system malformations including polymicrogyria and cerebellar hypoplasia (UniProt: Q9NTJ4). This disease link highlights the protein's importance in neurological development and function.

MAN2C1 is downregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.51 in post-mortem AD brain proteomics (Chaparral AD proteomics). The reduction in this glycoprotein degradation enzyme may reflect altered protein quality control mechanisms in AD pathology, though the functional consequence of decreased MAN2C1 levels in neurodegeneration remains to be established.