ABC-type oligopeptide transporter ABCB9

ABCB9 is an ATP-dependent oligopeptide transporter that mediates the translocation of peptides from the cytosol into the lysosomal lumen for degradation (UniProt: Q9NP78). The protein exhibits broad substrate specificity, transporting peptides ranging from 6 to at least 59 amino acids in length, with optimal activity at 23-mers. It shows preference for peptides with positively charged, aromatic, or hydrophobic residues at terminal positions.

ABCB9 is a member of the ABC transporter family and localizes to lysosomal membranes, where it participates in intracellular peptide homeostasis and protein quality control (UniProt: Q9NP78). The protein's role in lysosomal degradation pathways suggests involvement in cellular autophagy and clearance mechanisms that are fundamental to neural cell health.

In Alzheimer's disease, ABCB9 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.67 across subcellular fractions (Chaparral AD proteomics). This reduction in lysosomal peptide transport capacity may impair the clearance of proteolytic peptide products and contribute to protein aggregation pathology characteristic of AD.