Arl4d, a member of the ADP-ribosylation factor/ARF-like protein (ARF/ARL) family of Ras-related GTPases, plays crucial roles in multiple cellular processes. It functions in the regulation of cell morphology, cell migration, and actin cytoskeleton remodeling, and is involved in pathways such as microtubule nucleation, adipogenesis, and immune response regulation [1,2,4]. Genetic models, especially knockout (KO) mouse models, are valuable tools for studying Arl4d's functions.

In T cells, Arl4d-deficient CD4 T cells show enhanced IL-2 secretion, more efficient conversion into Foxp3 + induced regulatory T cells (iTreg) in vitro, and reduced colonic inflammation and lymphocytic infiltration in a transfer colitis model. This reveals that Arl4d restricts regulatory T-cell induction via control of IL-2 availability [5]. In addition, Arl4d-deficient CD8 T cells overproduce IL-2 upon stimulation, enhancing their expansion and effector function during viral infection in vivo, indicating its role in controlling T effector function by limiting IL-2 production [3].

In conclusion, Arl4d is involved in important biological processes including immune response regulation through its impact on IL-2 production and T-cell function. The study of Arl4d KO mouse models has provided insights into its role in diseases related to T-cell-mediated immune responses, such as colitis and viral infections, contributing to a better understanding of the underlying molecular mechanisms.