ADP-ribosylation factor (ARF)

ADP-ribosylation factor (ARF) is a family of small GTPases within the Ras superfamily, functionally characterized by their role as molecular switches cycling between GTP-bound (active) and GDP-bound (inactive) states[1][2][3]. When active, ARFs regulate intracellular membrane trafficking by recruiting cytosolic coat proteins for vesicle formation, remodeling actin, and modulating membrane lipid composition[1][2][3]. Several ARF isoforms (ARF1–ARF6 in humans) perform essential roles in the endoplasmic reticulum, Golgi apparatus, endosomes, and plasma membrane, integrating vesicular transport with cell signaling pathways[2][4]. Their signaling and functional activity are tightly controlled by GEFs (which activate ARFs by stimulating GDP-GTP exchange) and GAPs (which inactivate ARFs by stimulating GTP hydrolysis)[4][6][7]. ARF-regulated cellular functions—including vesicle trafficking, organelle structure, and actin cytoskeleton organization—are implicated in normal physiology and diseases such as cancer and inflammation[2][8]. Because of their central roles in these processes, ARFs are investigated as potential drug targets, but direct pharmacological inhibitors are not currently available for clinical use.

Other names

ARFArf-GTPaseADP-ribosylation factor GTPases

Modulation of ARF activity through regulation of GTP/GDP binding (by guanine nucleotide exchange factors [GEFs] and GTPase-activating proteins [GAPs]); Inhibition or activation of ARF-dependent vesicular trafficking; Indirect modulation of downstream signaling pathways related to cell proliferation and migration