ADP-ribosylation factor 4

ARF4 (ADP-ribosylation factor 4) is a small GTP-binding protein that functions as an allosteric activator of cholera toxin and plays a central role in intracellular protein trafficking (UniProt: P18085). It modulates vesicle budding and uncoating within the Golgi apparatus and participates in the ciliary targeting complex alongside Rab11, ASAP1, Rabin8, and RAB11FIP3 to direct preciliary vesicle trafficking during ciliogenesis.

ARF4 is widely distributed across cellular compartments involved in membrane transport and organelle organization. The UniProt annotation does not list primary disease associations, but the protein's role in vesicular trafficking implicates it in processes relevant to neuronal function and cell-autonomous homeostasis.

In Alzheimer's disease, ARF4 is downregulated in post-mortem AD brain relative to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.30 across a single subcellular fraction from TMT-labeled proteomics data. This modest but consistent reduction suggests potential dysregulation of vesicular trafficking in AD pathology, though the functional consequence requires further investigation.