PDLIM1, a member of the PDZ-LIM family, is a cytoskeletal protein. It functions as a platform to form distinct protein complexes, participating in multiple physiological processes such as cytoskeleton regulation, synapse formation, and autophagy during sperm development [1,5]. It is also involved in pathways like Hippo, Wnt, and β-catenin, playing a crucial role in various biological processes and diseases [2,3,6]. Genetic models, especially KO/CKO mouse models, could potentially provide in-depth insights into its function.

Functional studies have shown that PDLIM1 knockdown in hepatocellular carcinoma (HCC) cells induces epithelial-to-mesenchymal transition (EMT), increases invasive capacity, and promotes metastasis both in vitro and in vivo, while overexpression has opposite effects. PDLIM1 competitively binds to alpha-actinin 4 (ACTN4), preventing F-actin overgrowth and thus suppressing HCC metastasis by modulating Hippo signaling [2]. In diabetic retinopathy, PDLIM1 knockdown in retinal capillary endothelial cells treated with high-glucose and high-lipid medium promotes cell apoptosis, migration, and invasion by increasing Wnt3a levels [3]. In glioblastoma, PDLIM1 overexpression enhances cell proliferation, reduces apoptosis, increases glioblastoma stem cell proportions, and promotes chemoresistance and tumorigenesis, while knockdown inhibits these processes, likely through the PI3K-AKT pathway [4].

In conclusion, PDLIM1 is essential for regulating cytoskeleton-related functions and is involved in multiple disease-associated pathways. Studies using KO/CKO mouse models or other loss-of-function experiments, similar to the functional studies described, have revealed its role in cancer metastasis, diabetic retinopathy, and glioblastoma, providing potential therapeutic targets for these diseases.