CLDN1

CLDN1 encodes claudin-1, a tight junction membrane protein required for epithelial barrier function, as shown by claudin-1-deficient mice with severely affected epidermal barrier and neonatal death^[1]. Mechanistically, CLDN1 supports paracellular restriction in stratified epidermis and intestinal epithelium, where HIF-dependent CLDN1 regulation maintains tight junction integrity and barrier function^[2]. In disease models, reduced claudin-1 impairs human epidermal tight junction barrier function, induces IL-1β expression, and promotes inflammatory responses relevant to atopic dermatitis lesions^[3]. In viral entry models, CLDN1 acts as a hepatitis C virus co-receptor required for a late entry step after virus binding and CD81 interaction^[4][5]. Compared with related isoforms, CLDN6 and CLDN9 can support HCV entry in engineered cell lines, but monoclonal antibody studies show human hepatocyte infection does not depend on CLDN6 or CLDN9^[6]. For experimental applications, anti-CLDN1 monoclonal antibodies prevent HCV infection of primary human hepatocytes, while PDS-0330 binds claudin-1 and disrupts CLDN1/Src association in colorectal cancer models^[7][8].