The tale of two talins – two isoforms to fine‐tune integrin signalling

Talins are cytoplasmic adapter proteins essential for integrin-mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat-containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood. In this Review, we focus on the similarities and differences between the two talins in terms of structure, biochemistry and function, which hint at subtle differences in fine-tuning adhesion signalling.