Krt18, also known as Keratin 18, is one of the most abundant keratins in epithelial and endothelial cells. It has been implicated in various biological processes and is associated with multiple signaling pathways. It plays a significant role in cell proliferation, apoptosis, and cell adhesion, and its abnormal expression is related to the development of many diseases [3].

In embryo implantation, knockdown of Krt18 in mouse embryos inhibited embryo adhesion and implantation. In vitro experiments showed that silencing Krt18 disturbed trophoblast migration and invasion, and it was found that Krt18 directly binds to and stabilizes cell surface E-cadherin in trophoblast cells [1].

In colorectal cancer, down-regulation of Krt18 expression depressed CRC cell viability, migration and invasion, indicating its oncogenic role [2].

In gastric cancer, Krt18 knockdown in AGS cells promoted apoptosis and inhibited proliferation, and Krt18 was found to modulate alternative splicing of genes involved in proliferation and apoptosis processes [3].

In lung adenocarcinoma, Krt18 was significantly elevated, and its expression was correlated with poor clinical-pathological features and inferior prognostic outcome, and was associated with immune cell populations [5].

In urothelial papilloma, KRT18 was identified as a potential diagnostic biomarker, and its down-regulation was associated with subsequent progression to urothelial carcinoma [4].

In conclusion, Krt18 plays essential roles in embryo implantation, and is closely associated with the development and progression of several cancers such as colorectal, gastric, and lung adenocarcinoma, as well as in the diagnosis of urothelial papilloma. Loss-of-function experiments, especially in mouse models, have significantly contributed to revealing these functions, providing valuable insights into the biological processes and potential therapeutic targets in related diseases.