AbstractCell–matrix adhesion and cell–cell contacts are essential for the metabolism, protein synthesis, survival, and cancer metastasis of cells. Major transmembrane receptors are the integrins, which are responsible for cell–matrix adhesions, and the cadherins, which are important for cell–cell adhesions. Adherent cells anchor via focal adhesion proteins to the extracellular matrix, whereas cell–cell contacts connect via focal adherens junction proteins. The temporal formation of these connections is greatly strengthened either through externally applied stresses on the cell or by myosin‐driven cell contractility. The mechanism by which protein(s) within these connections sense, transmit, and respond to mechanochemical signaling is currently strongly debated and various candidates have been named. Vinculin has been described as one of the key players in cell–matrix and cell–cell adhesions that build a strong physical connection for transmitting forces between the cytoskeleton, the extracellular matrix, and cell–cell connections.