CARMIL1 (capping protein regulator and myosin 1 linker 1) is a multidomain membrane-cytoskeleton-associated protein that regulates actin polymerization dynamics and cell migration. Structurally, CARMIL1 comprises pleckstrin homology (PH), leucine-rich repeat (LRR), helical dimerization (HD), capping protein-binding region (CBR), and proline-rich (PR) domains 1. Its primary function involves binding to capping protein (CP) and allosterically weakening CP's affinity for actin filament barbed ends, thereby generating uncapped barbed ends and enhancing actin polymerization 1. CARMIL1 is partially autoinhibited, with mechanisms involving dimerization and an "antenna" motif that regulates its uncapping activity 1. Physiologically, CARMIL1 is essential for lamellipodial protrusion, ruffle formation, and macropinocytosis, but shows limited importance for cell migration in wound-healing models 2. Its LRR domain associates with IL-1 receptor signaling machinery and regulates inflammatory responses, including ERK activation and MMP expression 3. Beyond cytoskeletal functions, CARMIL1 promotes hepatocellular carcinoma proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway 4. Recent phosphoproteomic analysis reveals that C-terminal phosphorylation sites (T916, S968, S1067) influence actin dynamics through AKT1, PAK2, and other kinases 5. Clinically, CARMIL1 represents a novel IBD susceptibility locus with sex-dimorphic associations 6, and selective CARMIL1-AA inhibition blocks macropinocytosis in cancer cells without affecting autophagy 7.