ARL4D is a small GTPase that functions as a molecular switch regulating multiple cellular processes through GTP/GDP cycling 1. As a GTP-binding protein, ARL4D recruits cytohesins to the plasma membrane and promotes ARF6 activation to modulate actin cytoskeleton remodeling and cell migration 2. In its GTP-bound state, ARL4D interacts with EB1 in a GTP-dependent manner to promote centrosomal recruitment of EB1 and regulate microtubule nucleation 3. Conversely, GDP-bound ARL4D translocates to mitochondria where it alters mitochondrial morphology and membrane potential 4. TBC1D15 functions as an ARL4D GAP, promoting GTP hydrolysis and mitochondrial targeting under serum starvation to maintain organelle homeostasis 5. ARL4D expression is regulated by glucocorticoids in the brain, participating in actin cytoskeleton remodeling during stress responses 6. Aberrant ARL4D methylation and expression have been identified as significant contributors to breast cancer progression, with increased DNA methylation correlating inversely with gene expression 7. Additionally, ARL4D was identified as a key gene in cerebral ischemia-reperfusion injury response 8. These multifaceted roles position ARL4D as an important regulator of cytoskeletal dynamics, vesicular trafficking, and mitochondrial homeostasis.