Claudin-18 isoform 1 (CLDN18.1)

Claudin-18 isoform 1 (CLDN18.1) is a lung-specific member of the claudin family of transmembrane proteins, which are essential components of tight junctions that regulate paracellular permeability and maintain cell polarity (1.2.1, 1.5.1). It is primarily expressed in the alveolar epithelial cells (Type I and Type II) of the lung, where it plays a crucial role in maintaining the paracellular barrier and lung homeostasis (1.2.1, 2.5.5). In the context of oncology, CLDN18.1 is frequently downregulated in lung adenocarcinoma and is considered a tumor suppressor; its loss is associated with increased cell proliferation, activation of the IGF-1R/AKT signaling pathway, and poor patient prognosis (1.3.1, 2.2.1). While its sister isoform, CLDN18.2, is a major therapeutic target in gastric and pancreatic cancers, CLDN18.1 is primarily significant in drug development as a safety concern (1.1.4, 2.4.1). Due to the high sequence homology between the two isoforms—differing by only 7-8 amino acids in the first extracellular loop—therapeutic agents targeting CLDN18.2 must be carefully designed to avoid cross-reactivity with CLDN18.1 to prevent severe pulmonary toxicity (2.3.1, 2.5.4).

Other names

SFTA5SFTPJSurfactant associated protein JClaudin-18a1CLDN18 isoform 1

Maintenance of paracellular barrier; tumor suppression via inhibition of IGF-1R/AKT signaling