CLDN8 (claudin 8) is a tight junction protein that regulates paracellular transport and barrier function across multiple tissues. Structurally, CLDN8 cannot form tight junction strands independently but coassembles with other claudins, particularly CLDN4, to create anion-selective channels that facilitate paracellular chloride permeability in renal collecting ducts 1. In the epididymis, CLDN8 localizes to tight junctions across all segments and at epithelial cell interfaces, contributing to the blood-epididymal barrier critical for spermatozoal maturation 2. CLDN8 expression is significantly downregulated in inflammatory skin diseases. In atopic dermatitis and psoriasis, CLDN8 is among the tight junction markers that are substantially reduced 34. This downregulation is driven by AD-related cytokines (IL-4, IL-13, TNF-α, IFN-γ) that suppress CLDN8 through JAK signaling pathway activation 5. Notably, CLDN8 mRNA levels are restored following therapeutic interventions like dupilumab and crisaborole treatment 5. Beyond barrier function, CLDN8 exhibits oncogenic properties in cancer progression. In prostate cancer, CLDN8 is androgen-regulated and promotes cell proliferation and migration through effects on intracellular signaling and cytoskeleton stabilization 6. In colorectal and colon cancers, CLDN8 overexpression activates MAPK/ERK signaling to enhance proliferation, migration, and invasion 78. In Crohn's disease, dysregulation of the miR-145-5p/SOX9/CLDN8 pathway impairs intestinal mucosal barrier homeostasis 9.