MICALL2 (MICAL-like protein 2) is a cytoskeleton regulator and Rab GTPase effector involved in endocytic recycling and junctional complex assembly. It regulates the recycling of occludins, claudins, and E-cadherin to the plasma membrane, facilitating tight junction and adherens junction formation through actin cytoskeleton reorganization 1. MICALL2 undergoes liquid-liquid phase separation to organize tubular recycling endosomes in coordination with RAB8A. In cancer pathogenesis, MICALL2 promotes tumorigenesis through multiple mechanisms. In colorectal cancer, MICALL2 is upregulated and enhances cell growth and migration via Wnt/β-catenin signaling, while being negatively regulated by ubiquitin ligase TRIM21 1. In ovarian cancer, MICALL2 stabilizes EGFR through Rac1-dependent inhibition of lysosomal degradation, activating the EGFR-AKT-mTOR-MMP9 axis to promote invadopodia-mediated invasion 2. MICALL2 also promotes colorectal cancer angiogenesis via EGFR/PI3K/AKT/KLF5/VEGFA signaling 3. Beyond cancer, MICALL2 participates in epithelial-mesenchymal transition (EMT) in pulmonary fibrosis through NPAS2-regulated Wnt/β-catenin pathway activation 4, and represents a therapeutic target for liver fibrosis 5. MICALL2 is also implicated in ADHD pathogenesis, with reduced expression causing hyperactive-impulsive behavior in zebrafish 6. In myeloid leukemia, MICALL2 upregulation following 5-azacitidine treatment associates with improved survival 7.