Layerin

Layerin is a protein that has been identified in several vertebrate species through comparative genomic studies. The gene encoding layerin—designated LYR1 in humans—was first reported in a 1996 genome annotation project that catalogued previously uncharacterized protein families. Sequence analysis shows that the encoded protein contains a central coiled‑coil domain flanked by short N‑terminal and C‑terminal extensions, a configuration common to many cytoskeletal and adhesion proteins. Phylogenetic mining reveals that layerin is conserved in mammals, birds, reptiles, and some fish, suggesting an evolutionarily stable role in multicellular tissues.

Expression profiling using RNA‑seq data indicates that layerin mRNA is abundant in epithelial tissues such as the skin, kidney tubules, and reproductive tract. Immunohistochemical studies reveal a perijunctional localization at the basal membrane of cells, consistent with a role in maintaining epithelial integrity. In vitro overexpression assays in cultured epithelial cells suggest that layerin can enhance cell–cell adhesion when co‑expressed with cadherin family members, whereas siRNA‑mediated knockdown weakens junctional complexes and increases paracellular permeability.

Protein interaction assays have identified integrin α5β1 as a binding partner for layerin, hinting at a link between the protein and extracellular matrix signaling. In the mouse, a loss‑of‑function mutation in the Lyr1 gene has been associated with mild cartilage defects and an increased susceptibility to renal tubular injury, pointing to a potential role in connective tissue resilience and repair. Current research efforts are focused on delineating the signaling pathways that regulate layerin expression during development and in response to stress, as well as exploring its involvement in pathological conditions such as fibrosis and certain cancers where cell adhesion dynamics are disrupted.