Integrins are heterodimers of α- and β-subunits that regulate cell adhesion, migration, and extracellular matrix assembly. Their activation, mediated by intracellular signals, increases their affinity for extracellular ligands, enabling functions like platelet aggregation and leukocyte transmigration. Recent studies have identified talins and kindlins as key proteins that trigger integrin activation by interacting with their cytoplasmic domains. These proteins regulate integrin conformation and activation through structural and signaling interactions. The transmembrane domains of integrins play a critical role in transmitting signals across cell membranes, with structural features influencing their ability to activate. The activation process involves conformational changes and clustering of integrins, which can be influenced by intracellular signals and extracellular ligands. Talin and kindlin interactions are essential for integrin activation, with talin binding to β-integrin tails and kindlin interacting with β-integrin cytoplasmic domains. Mutations in these proteins can lead to defects in integrin function, as seen in diseases like leukocyte adhesion deficiency. Recent studies have also identified other proteins, such as RIAM, that facilitate integrin activation by recruiting talin to integrins. The activation of integrins is a complex process involving multiple signaling pathways and structural elements, with talin and kindlin playing central roles in regulating integrin function.Integrins are heterodimers of α- and β-subunits that regulate cell adhesion, migration, and extracellular matrix assembly. Their activation, mediated by intracellular signals, increases their affinity for extracellular ligands, enabling functions like platelet aggregation and leukocyte transmigration. Recent studies have identified talins and kindlins as key proteins that trigger integrin activation by interacting with their cytoplasmic domains. These proteins regulate integrin conformation and activation through structural and signaling interactions. The transmembrane domains of integrins play a critical role in transmitting signals across cell membranes, with structural features influencing their ability to activate. The activation process involves conformational changes and clustering of integrins, which can be influenced by intracellular signals and extracellular ligands. Talin and kindlin interactions are essential for integrin activation, with talin binding to β-integrin tails and kindlin interacting with β-integrin cytoplasmic domains. Mutations in these proteins can lead to defects in integrin function, as seen in diseases like leukocyte adhesion deficiency. Recent studies have also identified other proteins, such as RIAM, that facilitate integrin activation by recruiting talin to integrins. The activation of integrins is a complex process involving multiple signaling pathways and structural elements, with talin and kindlin playing central roles in regulating integrin function.