The article provides an overview of the integrin family, which are major cell adhesion receptors composed of α and β subunits. Integrins play crucial roles in cell-matrix interactions, tissue integrity, cell trafficking, and differentiation. The authors aim to clarify the complex landscape of integrin-ligand interactions, which have been identified through affinity chromatography, monoclonal antibody blocking, and direct protein-protein binding assays. Integrin-ligand pairs can be categorized into four main classes based on their structural basis: 1. **RGD-binding integrins**: These include αV, α5, α8, and αIIbβ3, which recognize ligands containing an RGD tripeptide. Crystal structures reveal that RGD binds at an interface between the α and β subunits. 2. **LDV-binding integrins**: These include α4β1, α4β7, α9β1, and members of the β2 sub-family. They bind to related sequences in their ligands, such as the LDV motif in fibronectin. 3. **A-domain β1 integrins**: These integrins, including α1, α2, α10, and α11, form a distinct laminin/collagen-binding subfamily. Crystal structures show that they bind collagen through a critical glutamate residue. 4. **Non αA-domain-containing laminin-binding integrins**: These include β1 integrins (α3, α6, α7) and α6β4, which bind to different regions of laminin. The article also discusses additional integrin-ligand interactions and highlights the evolutionary history of integrins, noting that early metazoans had a smaller complement of integrins compared to vertebrates. The authors acknowledge support from the Wellcome Trust and other institutions.The article provides an overview of the integrin family, which are major cell adhesion receptors composed of α and β subunits. Integrins play crucial roles in cell-matrix interactions, tissue integrity, cell trafficking, and differentiation. The authors aim to clarify the complex landscape of integrin-ligand interactions, which have been identified through affinity chromatography, monoclonal antibody blocking, and direct protein-protein binding assays. Integrin-ligand pairs can be categorized into four main classes based on their structural basis: 1. **RGD-binding integrins**: These include αV, α5, α8, and αIIbβ3, which recognize ligands containing an RGD tripeptide. Crystal structures reveal that RGD binds at an interface between the α and β subunits. 2. **LDV-binding integrins**: These include α4β1, α4β7, α9β1, and members of the β2 sub-family. They bind to related sequences in their ligands, such as the LDV motif in fibronectin. 3. **A-domain β1 integrins**: These integrins, including α1, α2, α10, and α11, form a distinct laminin/collagen-binding subfamily. Crystal structures show that they bind collagen through a critical glutamate residue. 4. **Non αA-domain-containing laminin-binding integrins**: These include β1 integrins (α3, α6, α7) and α6β4, which bind to different regions of laminin. The article also discusses additional integrin-ligand interactions and highlights the evolutionary history of integrins, noting that early metazoans had a smaller complement of integrins compared to vertebrates. The authors acknowledge support from the Wellcome Trust and other institutions.