The article discusses the classification and functional diversity of SF1 and SF2 helicases, which are essential enzymes involved in RNA and DNA metabolism. These helicases share a conserved catalytic core but exhibit diverse functions on various substrates. The study proposes a classification based on protein families, characterized by sequence, structural, and mechanistic features. This classification complements existing categorizations and highlights key structural and functional themes. The authors discuss recent data in the context of this unified view of SF1 and SF2 helicases. SF1 and SF2 helicases have a conserved core consisting of two similar domains resembling the RecA protein fold. This core contains characteristic sequence motifs that define the classification of helicases into superfamilies. The study identifies several families within SF1 and SF2, including the DEAD-box, Swi/Snf, and Pif1-like families. These families are distinguished by their sequence, structural, and mechanistic features. The study also explores the structural and functional characteristics of the helicase core, including the coordination of nucleic acid and NTP binding sites, and the role of specific motifs in unwinding mechanisms. The authors highlight the importance of family-typical mechanistic features in understanding the function of SF1 and SF2 helicases. The article also discusses the terminal accessory domains of helicases, which can influence or define the function of the enzyme. These domains often include nucleases, RNA or DNA binding domains, and domains involved in protein-protein interactions. The study concludes that significant progress has been made in understanding the structure-function relationships of SF1 and SF2 helicases. However, further research is needed to fully elucidate the mechanisms of these enzymes, particularly in physiological contexts. The authors emphasize the importance of integrating structural and mechanistic studies to gain a comprehensive understanding of helicase function.The article discusses the classification and functional diversity of SF1 and SF2 helicases, which are essential enzymes involved in RNA and DNA metabolism. These helicases share a conserved catalytic core but exhibit diverse functions on various substrates. The study proposes a classification based on protein families, characterized by sequence, structural, and mechanistic features. This classification complements existing categorizations and highlights key structural and functional themes. The authors discuss recent data in the context of this unified view of SF1 and SF2 helicases. SF1 and SF2 helicases have a conserved core consisting of two similar domains resembling the RecA protein fold. This core contains characteristic sequence motifs that define the classification of helicases into superfamilies. The study identifies several families within SF1 and SF2, including the DEAD-box, Swi/Snf, and Pif1-like families. These families are distinguished by their sequence, structural, and mechanistic features. The study also explores the structural and functional characteristics of the helicase core, including the coordination of nucleic acid and NTP binding sites, and the role of specific motifs in unwinding mechanisms. The authors highlight the importance of family-typical mechanistic features in understanding the function of SF1 and SF2 helicases. The article also discusses the terminal accessory domains of helicases, which can influence or define the function of the enzyme. These domains often include nucleases, RNA or DNA binding domains, and domains involved in protein-protein interactions. The study concludes that significant progress has been made in understanding the structure-function relationships of SF1 and SF2 helicases. However, further research is needed to fully elucidate the mechanisms of these enzymes, particularly in physiological contexts. The authors emphasize the importance of integrating structural and mechanistic studies to gain a comprehensive understanding of helicase function.