Alkyldihydroxyacetonephosphate synthase, peroxisomal

Alkyldihydroxyacetonephosphate synthase (AGPS) is a peroxisomal enzyme that catalyzes the exchange of acyl chains in acyl-DHAP for long-chain fatty alcohols, producing alkyl-DHAP as the first ether-linked intermediate in ether lipid biosynthesis (UniProt: O00116). The enzyme is expressed in human tissues involved in lipid metabolism and cellular signaling. Mutations in AGPS cause rhizomelic chondrodysplasia punctata type 3 (RCDP3), a severe genetic disorder marked by skeletal dysplasia, dwarfism, cataracts, and intellectual disability.

AGPS is associated with Alzheimer's Disease and shows significant downregulation in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics: mean log2 fold-change −0.62). This reduction was detected across subcellular fractions in TMT-labeled quantitative proteomics analysis of human AD brain samples. The downregulation of ether lipid biosynthesis machinery in AD suggests potential disruption of myelin composition and neuronal membrane integrity, which may contribute to neurodegeneration in Alzheimer's disease pathology.