MICAL2 is a flavin monooxygenase that functions as a redox-regulated actin cytoskeleton modifier with critical roles in cancer progression. As its primary function, MICAL2 catalyzes methionine oxidation of F-actin residues Met-44 and Met-47 to methionine-sulfoxide, promoting actin filament depolymerization and preventing repolymerization 1. The enzyme also regulates branched actin network disassembly by oxidizing ARP2/3 complexes 2. Mechanistically, MICAL2 mediates actin depolymerization-dependent nuclear actin oxidation, increasing MKL1/MRTF-A nuclear availability to enhance SRF:MKL1/MRTF-A-dependent transcription independent of RhoA 1. Regarding disease relevance, MICAL2 is significantly overexpressed in multiple cancers including pancreatic ductal adenocarcinoma, gastric cancer, renal cancer, and head and neck squamous cell carcinoma, where it promotes epithelial-mesenchymal transition (EMT), tumor growth, and metastasis 345. MICAL2 upregulates KRAS and EMT signaling pathways while activating ERK1/2 and AKT, and its ARG-mediated phosphorylation at Tyr445 and Tyr463 enhances its actin-depolymerizing capacity 35. Clinically, high MICAL2 expression correlates strongly with poor patient prognosis, positioning MICAL2 as a promising therapeutic target 3.