ILDR2

Immunoglobulin-like domain-containing receptor 2 (ILDR2), also termed Ig-like domain receptor 2, is a transmembrane protein implicated in cell-cell adhesion and signaling. Structurally characterized by immunoglobulin and fibronectin type III domains, ILDR2 interacts with polarity protein complexes to regulate planar cell polarity pathways, particularly in epithelial and neurosensory tissues. It modulates tight junction assembly and cytoskeletal dynamics through interactions with tricellulin and angulins, influencing tissue barrier integrity. Emerging evidence links ILDR2 to the Hippo signaling cascade, where it may govern organ size control and cell proliferation via cross-talk with YAP/TAZ transcriptional regulators.

Mutations in ILDR2 are associated with autosomal recessive nonsyndromic hearing loss (DFNB42), attributed to its critical role in cochlear hair cell stereocilia organization. Dysregulated ILDR2 expression has also been observed in epithelial cancers, potentially affecting metastasis through altered cell adhesion. While no targeted therapies exist, structural studies of its extracellular domain (PDB: 5XJM) have identified potential druggable interfaces. Preclinical models using adeno-associated virus-mediated gene replacement therapy show promise for hearing restoration, and small molecule modulators of ILDR2-mediated polarity pathways are under exploratory investigation for oncological applications.