The article provides an overview of the structure and function of nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins in plants, which are major components of the plant immune system. These proteins are encoded by large families of genes and can be divided into two subfamilies: TIR-domain-containing (TNL) and coiled-coil domain-containing (CNL). NBS-LRR proteins are involved in recognizing various pathogens, including bacteria, viruses, fungi, nematodes, insects, and oomycetes. They are characterized by a nucleotide-binding site (NBS) domain and a leucine-rich repeat (LRR) domain, with variable amino- and carboxy-terminal domains. The article discusses the evolutionary origins, genome organization, and structural features of NBS-LRR proteins, including the NBS and LRR domains. It highlights the role of these proteins in plant defense responses, such as the activation of oxidative bursts, calcium and ion fluxes, mitogen-associated protein kinase cascades, induction of pathogenesis-related genes, and the hypersensitive response. The article also explores the regulatory mechanisms that control NBS-LRR protein activity, including alternative splicing, phosphorylation, and protein degradation. Finally, it addresses several unresolved questions and future research directions, emphasizing the importance of understanding the evolutionary and functional aspects of NBS-LRR proteins for developing more durable plant disease resistance.The article provides an overview of the structure and function of nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins in plants, which are major components of the plant immune system. These proteins are encoded by large families of genes and can be divided into two subfamilies: TIR-domain-containing (TNL) and coiled-coil domain-containing (CNL). NBS-LRR proteins are involved in recognizing various pathogens, including bacteria, viruses, fungi, nematodes, insects, and oomycetes. They are characterized by a nucleotide-binding site (NBS) domain and a leucine-rich repeat (LRR) domain, with variable amino- and carboxy-terminal domains. The article discusses the evolutionary origins, genome organization, and structural features of NBS-LRR proteins, including the NBS and LRR domains. It highlights the role of these proteins in plant defense responses, such as the activation of oxidative bursts, calcium and ion fluxes, mitogen-associated protein kinase cascades, induction of pathogenesis-related genes, and the hypersensitive response. The article also explores the regulatory mechanisms that control NBS-LRR protein activity, including alternative splicing, phosphorylation, and protein degradation. Finally, it addresses several unresolved questions and future research directions, emphasizing the importance of understanding the evolutionary and functional aspects of NBS-LRR proteins for developing more durable plant disease resistance.