Arf6, also known as ADP-ribosylation factor 6, is a small G-protein of the Ras superfamily. It plays pivotal roles in multiple cellular events such as exocytosis, endocytosis, actin remodeling, plasma membrane reorganization, and vesicular transport. It is involved in various pathways like the CLIC4/Arf6 pathway, and its activation is associated with many biological processes and disease conditions [1,3].

Arf6 has been implicated in numerous disease-related processes. In cancer, its activation promotes cell motility, invasion, and metastasis in tumors like breast, pancreatic, and lung cancer, and it may cooperate with KRAS and MYC to enhance cancer malignancy and immune evasion [1,4,5]. In the context of pulmonary hypertension, Arf6 is a novel effector of CLIC4 and a potential therapeutic target [3]. In the central nervous system, ARF6 activation prevents integrin axonal transport in mature CNS axons, reducing regenerative ability, thus making it a potential target for promoting axon regeneration after CNS injury [2]. In host-pathogen interactions, Arf6 is used for pathogen phagocytosis and can be targeted by pathogens. It also plays a role in the entry and infection of SARS-CoV-2 [6,7]. Additionally, in endometriosis, high expression of Arf6 in ectopic endometrial epithelial cells leads to mitochondrial membrane-marginalization and induces epithelial-mesenchymal transition, which is involved in the disease's pathogenesis [8].

In conclusion, Arf6 is crucial for various cellular functions and is deeply involved in multiple disease areas such as cancer, pulmonary hypertension, CNS injury-related regeneration, host-pathogen interactions, and endometriosis. Understanding its functions through various research models contributes to a better understanding of disease mechanisms and the development of potential therapeutic strategies.