Vang-like protein 2 (VANGL2) (VANGL2)

Vang-like protein 2 (VANGL2) is a highly conserved four-pass transmembrane protein that serves as a core component of the non-canonical Wnt/planar cell polarity (PCP) signaling pathway. It plays a critical role in coordinating the orientation of cells within a tissue plane, which is essential for processes such as neural tube closure, inner ear development, and directed cell migration (UniProt, 2024). Mutations in the VANGL2 gene are strongly associated with severe neural tube defects, including craniorachischisis, in both animal models and humans (PubMed, 2021). In the context of oncology, VANGL2 is frequently overexpressed in various malignancies, where it promotes epithelial-mesenchymal transition (EMT), cell invasion, and metastasis by modulating the actin cytoskeleton and interacting with proteins like Dishevelled (DVL) (NIH, 2023). While there are currently no FDA-approved drugs specifically targeting VANGL2, it is an area of active research for therapeutic intervention, particularly using RNA-based strategies like siRNA or antisense oligonucleotides to downregulate its expression in metastatic cancers (PubMed, 2022). Therapeutic challenges include the potential for off-target effects on normal tissue architecture and the necessity of precise delivery to avoid systemic developmental toxicity.

Other names

Van Gogh-like protein 2Strabismus homolog 1STB1STBMLPP1LTAP

Inhibition of VANGL2 protein expression through mRNA-targeted degradation (e.g., via siRNA or antisense oligonucleotides) or disruption of protein-protein interactions such as the VANGL2-Dishevelled (DVL) complex.