Talin has a key role in integrin-dependent adhesion of cells to the extracellular matrix, and Kashina and colleagues now report that talin also mediates cell–cell adhesion. A 70 kDa carboxy-terminal fragment (termed VAD) of talin was seen in several cell types and localized at cadherin-containing cell–cell adhesion sites. This fragment was generated through cleavage of talin by the protease calpain 2, and cleavage was dependent on arginylation of VAD. Importantly, arginylation-deficient mutant cells that lacked the VAD fragment formed fewer and smaller cell–cell adhesions, indicating a role for VAD in cell–cell contacts. Furthermore, arginylation was integral in the regulation of VAD function, as arginylated VAD was more efficient in forming cell–cell contacts than its non-arginylated counterpart. Thus, this work uncovers a new role of talin in cadherin-dependent cell–cell adhesion and highlights arginylation as an important post-translational modification.