Claudin-1 (CLDN1) (CLDN1)

Claudin-1 is a 22 kDa transmembrane protein that serves as a primary structural component of tight junction strands, which regulate the paracellular movement of water, ions, and small molecules across epithelial barriers (UniProt P56744). It is essential for maintaining cell polarity and the integrity of the blood-tissue barrier in various organs, including the skin and liver (PubMed: 9647613). Beyond its physiological role, Claudin-1 is a critical entry factor for the Hepatitis C virus (HCV), acting as a co-receptor that facilitates viral internalization into hepatocytes (PubMed: 17325670). In oncology, Claudin-1 is often overexpressed in certain solid tumors, where it promotes epithelial-to-mesenchymal transition (EMT) and tumor progression, while its loss in other contexts can impair barrier function and promote inflammation (PubMed: 26549031). Therapeutic candidates like ALE.C04 and ALE.F02 are monoclonal antibodies designed to target Claudin-1 for the treatment of cancer and fibrotic diseases by inhibiting its pathological signaling and structural roles (Alentis Therapeutics). However, targeting this protein carries risks of systemic toxicity, particularly skin-related issues like ichthyosis, due to its widespread role in maintaining the epidermal barrier (PubMed: 12110603).

Other names

CLDN1SEMP1Senescence-associated epithelial membrane protein 1Tight junction protein CLDN1

Monoclonal antibodies targeting Claudin-1 function by blocking the interaction between the protein and its ligands or viral partners, such as the Hepatitis C virus envelope proteins, thereby preventing viral entry (PubMed: 17325670). In the context of cancer and fibrosis, these antibodies may disrupt pathological signaling complexes, such as those involving the Wnt/beta-catenin pathway, or modulate the epithelial-to-mesenchymal transition (EMT) to inhibit tumor progression and fibrotic remodeling (Alentis Therapeutics; PubMed: 26549031).