The dual role of kindlin-2 in mechanotransduction: A bridge for sensing and a hub for signaling.

The bidirectional communication between the cell and the extracellular mechanical microenvironment established by integrins and various adhesion proteins is a well-established paradigm of mechanotransduction. Kindlin-2, belonging to the 4.1-ezrin-ridixin-moesin (FERM) domain family of proteins, has emerged as a key mechanosensitive protein. Here, we start with the unique structure of kindlin-2, then review the performance of kindlin-2 in mechanotransduction by focusing on its two potential modes of function: as a physical structure for mechanosensing and as a member of multiple pathways for mechanosignaling. Finally, we discuss the relationship between kindlin-2 and pathological states associated with an aberrant mechanical microenvironment. We hope the discussions around kindlin-2 can establish a theoretical framework for regarding kindlin-2 as a mechanomedicine target in future therapeutic research.