CRB2 is an apical polarity protein that maintains epithelial cell organization and functions across multiple tissues. In the retina, CRB2 co-localizes and forms homo- and heteromeric complexes with CRB1, playing essential roles in photoreceptor organization, layer thickness, and structural integrity 1. CRB2 also contributes to retinal homeostasis through mechanisms that may determine cone photoreceptor outer segment length 1. In developing tissues, CRB2 promotes epithelial-to-mesenchymal transition during gastrulation by facilitating cell ingression into the embryo [UniProt]. CRB2 maintains apical polarity complexes during cortical development and plays a critical role in podocyte mechanotransduction; CRB2 depletion impairs mechanosensing through disrupted YAP signaling and enhanced contractility at low substrate stiffness 2. Pathogenic CRB2 variants cause CRB2-related syndrome, characterized by ventriculomegaly, nephrotic syndrome, and cardiac abnormalities 34. CRB2 mutations cause steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis through podocyte dysfunction 2. CRB2 is also associated with retinitis pigmentosa 1. Beyond developmental roles, CRB2 acts as an epigenetic ferroptosis regulator in head and neck squamous cell carcinoma, with CRB2 upregulation correlating with improved prognosis and sensitizing cancer cells to ferroptosis 5.