The claudins (CLDNs; with 23 genes in humans) are a family of tetra-transmembrane proteins.
Proposed classification, from review [5]
CLDNs 1, 3, 4, 5, 6, 7, 9, 11, 14, 18.1 and 19 form autonomous tight junction barriers.
CLDNs 2, 10a, 10b and 15 form autonomous tight-junction-barrier-based paracellular channels.
CLDNs 8, 12, 16, 17, and 20-25 form nonautonomous tight junction barriers.
CLDN-18.2 forms an acid-enhancible tight junction barrier.

CLDNs are integral components of tight junctions with roles in barrier integrity, channel permeability and epithelial tissue organisation at the cellular level. They have tissue-specific physiological roles, and expression can be dysregulated in tumours of epithelial origin [3,5,7-8,10-13], and can be considered as prognostic markers or as therapeutic targets.

The first claudin-targeted drug to be approved was zolbetuximab (in 2024), which binds CLDN18.2, and is used to treat advanced 18.2+ve gastric and gastroesophageal cancers.

The claudins (CLDNs; with 23 genes in humans) are a family of tetra-transmembrane proteins that are involved in regulating epithelial function. They are integral components of tight junctions with roles in barrier integrity, channel permeability and epithelial tissue organisation at the cellular level. Claudins have tissue-specific physiological roles, and expression can be dysregulated in tumours of epithelial origin. Approval of the first claudin-targeting drug, zolbetuximab (anti-CLDN18.2), in 2024 signalled the interest in the devlopment of agents that target CLDNs for therapeutic potential [1-2,4-6].

1. Balsa M, Alonso S, Sánchez L, Bugés C, Layos L, Calvo M, Garsot E, Viciano M, Clavell A, López R et al.. (2026) Targeting claudins in gastric cancer: A novel GLOWing strategy in the SPOTLIGHT. Cancer Treat Rev, 146: 103141. [PMID:42035746]

2. Hana C, Thaw Dar NN, Galo Venegas M, Vulfovich M. (2024) Claudins in Cancer: A Current and Future Therapeutic Target. Int J Mol Sci, 25 (9). [PMID:38731853]

3. Huang S, Zhang J, Li Y, Xu Y, Jia H, An L, Wang X, Yang Y. (2023) Downregulation of Claudin5 promotes malignant progression and radioresistance through Beclin1-mediated autophagy in esophageal squamous cell carcinoma. J Transl Med, 21 (1): 379. [PMID:37303041]

4. Nakayama I, Qi C, Chen Y, Nakamura Y, Shen L, Shitara K. (2024) Claudin 18.2 as a novel therapeutic target. Nat Rev Clin Oncol, 21 (5): 354-369. [PMID:38503878]

5. Niwa Y, Matsushita S, Nakayama I, Kondoh M. (2026) Targeting claudins in cancer. Nat Rev Drug Discov, Epub ahead of print. DOI: 10.1038/s41573-026-01450-2

6. Osanai M, Takasawa A, Murata M, Sawada N. (2017) Claudins in cancer: bench to bedside. Pflugers Arch, 469 (1): 55-67. [PMID:27624415]

7. Paes MF, Zipinotti Dos Santos D, Massariol Pimenta T, Ribeiro Junior RS, da Silva Martins B, Greco SJ, Carvalho AA, Bacchi C, Duarte C, Carvalho Í et al.. (2023) Overexpression of CLDN16 in ovarian cancer is modulated by PI3K and PKC pathways. Exp Cell Res, 426 (2): 113523. [PMID:36889572]

8. Rahman A, Kobayashi M, Sugimoto K, Endo Y, Kojima M, Furukawa S, Watanabe T, Soeda S, Hashimoto Y, Fujimori K et al.. (2021) Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer. Int J Mol Sci, 22 (7). [PMID:33917356]

9. Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, Huber C, Türeci O. (2008) Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res, 14 (23): 7624-34. [PMID:19047087]

10. Wang DW, Zhang WH, Danil G, Yang K, Hu JK. (2022) The role and mechanism of claudins in cancer. Front Oncol, 12: 1051497. [PMID:36620607]

11. Watanabe M, Higashi T, Ozeki K, Higashi AY, Sugimoto K, Mine H, Takagi H, Ozaki Y, Muto S, Okabe N et al.. (2021) CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma. Sci Rep, 11 (1): 12554. [PMID:34131154]

12. Xu J, Chen M, Hu M, Wang H, Zuo Z, Wang J, Xie Z. (2022) Claudin 19 inhibits the malignant potential of breast cancer cells by modulating extracellular matrix-associated UBE2C/Wnt signaling. Am J Cancer Res, 12 (12): 5552-5563. [PMID:36628278]

13. Yang L, Zhang W, Li M, Dam J, Huang K, Wang Y, Qiu Z, Sun T, Chen P, Zhang Z et al.. (2022) Evaluation of the Prognostic Relevance of Differential Claudin Gene Expression Highlights Claudin-4 as Being Suppressed by TGFβ1 Inhibitor in Colorectal Cancer. Front Genet, 13: 783016. [PMID:35281827]