Ckap4, also known as Cytoskeleton Associated Protein 4, is an endoplasmic reticulum protein present in the cell surface membrane [1,4,6]. It acts as a receptor for proteins like Dickkopf-1 (DKK1), Dickkopf-3 (DKK3), and is involved in multiple pathways. It plays roles in regulating cell adhesion, migration, and is associated with various biological processes such as reticulophagy, mitochondrial functions, and fibroblast activation [1,2,4,5,6].

In glioblastoma cells, Ckap4 knockdown reduced malignant potential, while overexpression increased Forkhead Box M1 (FOXM1) expression along with elevated AKT and ERK phosphorylation, indicating its role in glioblastoma malignancy [1]. In hepatocellular carcinoma, Ckap4 competitively binds to RETREG1, regulating its degradation and reticulophagy, and its oncogenic potential was demonstrated in animal models [2]. In lung cancer, Ckap4 was released with exosomes, and its overexpression promoted cell proliferation, which was inhibited by an anti-Ckap4 antibody. The combination of this antibody and osimertinib showed stronger anti-tumor effects [3].

In conclusion, Ckap4 is crucial in multiple biological processes and is involved in the progression of various cancers including glioblastoma, hepatocellular carcinoma, and lung cancer. Studies using gene-knockdown models have been instrumental in revealing its role in these disease conditions, providing potential therapeutic targets for treatment.