Integrins are large, membrane-spanning, heterodimeric proteins essential for metazoan survival. They consist of α and β subunits, with 18 α and 8 β subunits forming 24 different receptors. The ectodomains of integrins have a "bent" conformation, with ligand-binding sites near the membrane surface. Structural studies reveal that integrins have flexible domains, including the α-I domain, which can undergo conformational changes affecting binding affinity. The β-I domain also plays a role in ligand binding, with cations like Mg²⁺, Ca²⁺, and Mn²⁺ influencing this process. The transmembrane (TM) segments of integrins are involved in receptor activation, with the α IIb β3 TM complex showing a structure where the α IIb helix is perpendicular to the membrane and the β3 helix is tilted. The cytoplasmic tails of integrins interact with proteins like talin and kindlin, which are crucial for activation. The β tail domain contains a β-sandwich fold and is involved in signaling. Structural studies of intact integrins suggest that activation involves conformational changes, such as the swing-out of the hybrid domain, leading to an upright conformation. Ligand binding is regulated by conformational changes, with RGD and LDV motifs being important for recognition. Integrin activation is essential for cell signaling and adhesion, and involves conformational changes that allow ligand binding. Anti-integrin monoclonal antibodies can inhibit ligand binding by stabilizing the unoccupied state or preventing conformational changes. Recent studies have provided insights into integrin structure, activation, and function, highlighting the importance of conformational changes in regulating integrin activity. The review summarizes recent progress in understanding integrin structure, activation, and interactions, emphasizing the role of conformational changes in signaling and adhesion.Integrins are large, membrane-spanning, heterodimeric proteins essential for metazoan survival. They consist of α and β subunits, with 18 α and 8 β subunits forming 24 different receptors. The ectodomains of integrins have a "bent" conformation, with ligand-binding sites near the membrane surface. Structural studies reveal that integrins have flexible domains, including the α-I domain, which can undergo conformational changes affecting binding affinity. The β-I domain also plays a role in ligand binding, with cations like Mg²⁺, Ca²⁺, and Mn²⁺ influencing this process. The transmembrane (TM) segments of integrins are involved in receptor activation, with the α IIb β3 TM complex showing a structure where the α IIb helix is perpendicular to the membrane and the β3 helix is tilted. The cytoplasmic tails of integrins interact with proteins like talin and kindlin, which are crucial for activation. The β tail domain contains a β-sandwich fold and is involved in signaling. Structural studies of intact integrins suggest that activation involves conformational changes, such as the swing-out of the hybrid domain, leading to an upright conformation. Ligand binding is regulated by conformational changes, with RGD and LDV motifs being important for recognition. Integrin activation is essential for cell signaling and adhesion, and involves conformational changes that allow ligand binding. Anti-integrin monoclonal antibodies can inhibit ligand binding by stabilizing the unoccupied state or preventing conformational changes. Recent studies have provided insights into integrin structure, activation, and function, highlighting the importance of conformational changes in regulating integrin activity. The review summarizes recent progress in understanding integrin structure, activation, and interactions, emphasizing the role of conformational changes in signaling and adhesion.