MICAL3 is a flavin-containing monooxygenase that regulates actin cytoskeleton dynamics through redox-dependent mechanisms. Its primary function involves catalyzing oxidation of specific methionine residues on F-actin to methionine-sulfoxide, promoting actin filament depolymerization 1. The enzyme contains conserved flavin adenine dinucleotide (FAD)/NADPH-binding and calponin-homology domains that work cooperatively, with catalytic efficiency dramatically increasing upon F-actin binding 1. In the absence of actin substrates, MICAL3 functions as a NADPH oxidase producing hydrogen peroxide 2. Beyond cytoskeletal remodeling, MICAL3 acts as a Rab effector protein critical for exocytic vesicle trafficking. It cooperates with Rab6 and Rab8A to mediate docking and fusion of secretory carriers at the plasma membrane, with its monooxygenase activity regulating protein complex turnover 3. MICAL3 is essential for cytokinesis, promoting recruitment of Rab8 and ERC1 to intercellular bridges to facilitate timely abscission 4. During early development, CHK1 interaction with MICAL3 regulates pronuclear envelope breakdown by controlling F-actin disassembly 4. Clinically, MICAL3 dysregulation associates with neurodegenerative diseases. It shows differential expression in multiple sclerosis 5 and represents a candidate biomarker for Parkinson's disease diagnosis, particularly through HbA1c-related mechanisms 6. Genetic variants in MICAL3 constitute shared risk factors across alpha-synucleinopathies, implicating RhoA/actin pathway dysfunction in disease pathogenesis 7.