Crb3, short for Crumbs homolog 3, is an apical polarity protein. It plays essential roles in cell polarity regulation, a key aspect in numerous biological processes such as cell growth, migration, and molecular transport. Crb3 is involved in ciliogenesis, regulating the γ -tubulin ring complex (γTuRC) assembly via Rab11-mediated vesicle trafficking, and is associated with cilium-related Hh and Wnt signaling pathways [1]. It also contributes to organizing the apical domain of multiciliated cells, which is crucial for centrioles/BBs migration and ciliogenesis [2].

Crb3 knockout mice exhibit severe primary cilium defects in the mammary ductal lumen and renal tubule. Mammary epithelial-specific Crb3 knockout mice show ductal epithelial hyperplasia and tumorigenesis promotion, highlighting its significance in lumen formation and ciliary assembly in the mammary epithelium [1]. In addition, in breast cancer, knockdown of Crb3 in non-tumorigenic breast epithelial cells confers cancer stem cell properties, and downregulation of Crb3 in human breast cancer tissues is observed [3]. In clear cell renal cell carcinoma, methylation of Crb3 is related to its reduced expression, clinicopathological parameters, and poor prognosis [4].

In conclusion, Crb3 is vital for maintaining normal cell functions like ciliogenesis and cell polarity. The study of Crb3 knockout and conditional knockout mouse models has provided valuable insights into its role in diseases such as breast cancer and clear cell renal cell carcinoma, emphasizing its potential as a biomarker and therapeutic target in these disease areas.