Significance Metastasis remains the major cause of cancer-related deaths. Overactivation of receptor tyrosine kinase AXL has been correlated with cancer invasion and metastasis, resistance to therapies, and poor patient prognosis. However, the cellular processes activated by AXL and its ligand, GAS6, are largely unknown. Here, we identified a proximity interactome of AXL and revealed actin-dependent processes activated by GAS6-AXL, including membrane ruffling and macropinocytosis, that provide insights into the role of AXL in cancer progression. The identified AXL interactors can be used in translational research toward development of effective therapies for metastatic and/or chemoresistant cancers with AXL overactivation. Moreover, our data provide a mechanistic explanation for previous studies reporting that AXL might contribute to macropinocytic uptake of viruses.