LIMK2, a serine-specific kinase, is a 72 kDa protein that regulates actin and cytoskeleton reorganization, playing a crucial role in the Rho family GTPase signal transduction pathways [1,3]. It phosphorylates cofilin to inactivate it, allowing actin polymerization, which is essential for cell cycle progression, apoptosis, and migration [1]. LIMK2 is involved in numerous biological processes such as cell cycle, cell migration, and neuronal differentiation, and is associated with many pathological mechanisms, especially in cancer [3]. Genetic models, like KO/CKO mouse models, can be valuable for studying its functions.

In cancer research, inducible knockdown of LIMK2 fully reverses tumorigenesis in castration-resistant prostate cancer (CRPC) in castrated mice, highlighting its potential as a clinical target for CRPC [6]. In melanoma, genetic or pharmacological inhibition of LIMK2 impairs tumor growth and metastasis in cell culture and mice [2]. In triple-negative breast cancer (TNBC), shRNA-mediated LIMK2 knockdown or its pharmacological inhibition blocks metastatic attributes of TNBC cells [5]. In airway smooth muscle, LIMK2-deficient ASMs show approximately 30% inhibition in maximal force, and LIMK2 deletion causes a significant decrease in cofilin phosphorylation and F/G-actin ratio, indicating its necessity for F-actin dynamics and force transduction [4].

In conclusion, LIMK2 is essential for regulating actin and cytoskeleton reorganization, participating in multiple biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in various cancer types like CRPC, melanoma, and TNBC, as well as in airway smooth muscle function. These findings suggest LIMK2 could be a potential therapeutic target in certain diseases.