ARFIP2 is a multifunctional protein that coordinates vesicular trafficking and cellular homeostasis through several interconnected pathways. Primarily, ARFIP2 regulates constitutive metalloproteinase secretion from the trans-Golgi network, particularly for MMP7 and MMP2, through its role in cargo subdomain-specific vesicle biogenesis 1. ARFIP2 functions as a critical regulator of autophagy by controlling starvation-dependent ATG9A vesicle trafficking that delivers PI4KB to autophagosome initiation sites 23. During mitophagy, ARFIP2 facilitates ATG9A trafficking to mitochondria to promote phagophore growth 4. Recently, ARFIP2 was shown to regulate lysosomal repair by coordinating PI4K2A delivery via ATG9A vesicles and sequestering PI4P on damaged lysosomes 5. ARFIP2 also participates in NF-κB inhibition through interactions with IKBKB and IKBKG 6. Clinically, low ARFIP2 expression correlates with poor prognosis in breast cancer and trastuzumab resistance 7, while ARFIP2 deficiency impairs autophagy and mitophagy in podocytes, exacerbating diabetic nephropathy 8. ARFIP2 knockdown inhibits hepatocellular carcinoma cell proliferation and migration 9, suggesting therapeutic potential across multiple cancer types.