Cingulin-like protein 1

Cingulin-like protein 1 (CGNL1) is a 1,302-amino acid protein that may anchor the apical junctional complex, particularly tight junctions, to actin-based cytoskeletons (UniProt: Q0VF96). This cytoskeletal-anchoring function positions it at cell–cell interfaces where barrier integrity is maintained.

CGNL1 is associated with aromatase excess syndrome (AEXS, MIM 139300), an autosomal dominant disorder affecting steroid metabolism (UniProt: Q0VF96). Beyond this monogenic association, the protein's role in junction stability suggests potential relevance to epithelial and endothelial barriers in various tissues.

CGNL1 shows elevated abundance in Alzheimer's disease: it is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change +0.62, Chaparral AD proteomics), based on TMT-labeled quantitative proteomics across four subcellular fractions. This upregulation may reflect compensatory responses or pathological changes in neuronal barriers associated with neurodegeneration.