ADP-ribosylation factor-binding protein GGA2

GGA2 (ADP-ribosylation factor-binding protein GGA2) is a 613-amino acid adaptor protein that mediates protein sorting and trafficking between the trans-Golgi network and endosomes (UniProt: Q9UJY4). It recruits clathrin to the TGN in an ARF-dependent manner, binds ubiquitinated cargo molecules, and regulates retrograde transport of phosphorylated BACE1 from endosomes back to the trans-Golgi network.

GGA2 functions in vesicular transport pathways critical for protein delivery and receptor trafficking, including regulation of GPCR surface expression. Its role in BACE1 retrograde transport connects it to amyloid-β metabolism, a central feature of Alzheimer's disease pathology.

In Alzheimer's disease, GGA2 is downregulated in human post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.55; Chaparral AD proteomics). This reduced expression was detected across subcellular fractions in a TMT-labeled proteomics study, suggesting potential impairment of the endosomal-trans-Golgi retrograde trafficking pathway in AD brain.