LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies.

LIMK2, a serine-specific kinase, was discovered as an actin dynamics regulating kinase. Emerging studies have shown its pivotal role in numerous human malignancies and neurodevelopmental disorder. Inducible knockdown of LIMK2 fully reverses tumorigenesis, underscoring its potential as a clinical target. However, the molecular mechanisms leading to its upregulation and its deregulated activity in various diseases largely remain unknown. Similarly, LIMK2's peptide substrate specificity has not been analyzed. This is particularly important for LIMK2, a kinase almost three decades old, as only a handful of its substrates are known to date. As a result, most of LIMK2's physiological and pathological roles have been assigned to its regulation of actin dynamics via cofilin. This review focuses on LIMK2's unique catalytic mechanism, substrate specificity and its upstream regulators at transcriptional, post-transcriptional and post-translational stages. Moreover, emerging studies have unveiled a few tumor suppressors and oncogenes as LIMK2's direct substrates, which in turn have uncovered novel molecular mechanisms by which it plays pleiotropic roles in human physiology and pathologies independent of actin dynamics.