CRB3 is a cell polarity protein essential for establishing and maintaining epithelial cell organization. Functionally, CRB3 localizes to the apical plasma membrane and tight junctions, where it regulates morphogenesis and organization of these structures 12. CRB3 operates through multiple mechanisms: it promotes phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and TAZ, suppressing TGFB1-dependent transcription [UniProt annotation]. Additionally, CRB3 navigates Rab11-positive trafficking vesicles to promote γ-tubulin ring complex assembly during ciliogenesis, localizing to the basal body 3. At the Golgi, CRB3 sorting is regulated by a size filter mechanism; its small cytoplasmic domain facilitates apical trafficking, and timely dissociation of its binding partner Pals1 is essential for normal transport 4. Developmentally, CRB3 is transported by dynein to maintain apical radial glial cell processes and prevent inappropriate neural progenitor delamination 5. Clinically, CRB3 dysfunction associates with disease: its reduced expression correlates with tamoxifen resistance in breast cancer through β-catenin pathway activation 6, while CRB3 restoration suppresses cancer stemness 6. CRB3 expression alterations appear relevant to multiple sclerosis pathophysiology through Hippo pathway dysregulation 7. CRB3 loss also causes severe primary cilium defects and promotes epithelial tumorigenesis 3.