RUFY3 (RUN and FYVE domain containing 3) functions as an ARL8 effector protein that regulates endolysosome transport and cellular migration. The protein promotes coupling of endolysosomes to dynein-dynactin complexes for retrograde transport along microtubules 1. In non-neuronal cells, RUFY3 concentrates endolysosomes in the juxtanuclear area, while in hippocampal neurons, it drives retrograde transport from axons to soma 1. RUFY3 also serves as a noncanonical guanine nucleotide exchange factor for Rab5, regulating endocytosis-coupled focal adhesion turnover and cell migration 2. Additionally, RUFY3 interacts with the JIP4-dynein-dynactin complex to regulate lysosome size and positioning 3. The protein plays important roles in cytoskeletal organization by promoting F-actin-enriched protrusive structure formation at cell periphery 4. In cancer contexts, RUFY3 exhibits oncogenic properties, promoting epithelial-mesenchymal transition and metastasis in colorectal, gastric, and hepatocellular cancers 546. Paradoxically, low RUFY3 expression is associated with lymph node metastasis in older women with breast cancer 7, suggesting tissue-specific roles in cancer progression.