ARL2 is a small GTPase that cycles between inactive GDP-bound and active GTP-bound states, regulating diverse cellular processes through interaction with guanine nucleotide exchange factors and GTPase-activating proteins 1. Primary functions include regulation of microtubule dynamics and centrosome integrity, where ARL2 antagonizes TBCD-mediated microtubule destruction and participates in centrosome cohesion through a pathway involving ELMOD2 and Rootletin 23. ARL2 localizes to mitochondria and regulates mitochondrial fusion and integrity, binding the adenine nucleotide transporter ANT1 42. Additionally, ARL2 mediates trafficking of lipidated cargo to cilia via PDE6δ and Unc119 carriers 1. In the nucleus, ARL2 promotes homologous recombination repair by coordinating RAD51 family gene expression, critical for colon cancer stem cell survival 5. Disease relevance is substantial: ARL2 is downregulated in glioma yet upregulated in cervical cancer, where miR-214 suppresses proliferation by targeting ARL2 67. In Alzheimer's disease, ARL2 represents an APOE-ε4-dependent protein signature, being downregulated by APOE-ε4 yet paradoxically upregulated with disease onset, suggesting a compensatory response to neurodegeneration 8. These multifunctional roles position ARL2 as a potential therapeutic target across multiple cancer types and neurodegenerative diseases.