Claudin-1 (exposed non-junctional form) (CLDN1)

Claudin-1 (CLDN1) is a transmembrane protein that typically functions as a primary structural component of tight junctions, where it regulates the paracellular transport of ions and solutes between epithelial cells (UniProt P56748). In healthy physiological conditions, CLDN1 is sequestered within these junctions and is not accessible to the extracellular environment. However, in certain pathological conditions such as cancer and organ fibrosis, CLDN1 is overexpressed and localized to the non-junctional plasma membrane, becoming “exposed” and accessible to therapeutic agents (Alentis Therapeutics, 2024). This non-junctional form of CLDN1 plays a significant role in disease progression by promoting the epithelial-mesenchymal transition (EMT), cell survival, and myofibroblast activation (PubMed: 33053355). Therapeutic antibodies like ALE.C04 and ALE.F02 are designed to selectively target this exposed form, offering a precision medicine approach to treat solid tumors and fibrotic diseases while minimizing damage to healthy tissues where CLDN1 remains protected within tight junctions (Nature Communications, 2022).

Other names

CLDN1Senescence-associated epithelial membrane protein 1SEMP1Exposed Claudin-1

Monoclonal antibodies specifically bind to the extracellular loops of Claudin-1 when it is expressed outside of tight junctions (non-junctional form), leading to immune-mediated cytotoxicity (ADCC/CDC) in cancer or the reversal of fibrotic signaling in myofibroblasts (Alentis Therapeutics, 2024; Nature Communications, 2022).