The study introduces lncRNA Homology Explorer (lncHOME), a computational pipeline that identifies long noncoding RNAs (lncRNAs) with conserved genomic locations and patterns of RNA-binding protein (RBP) binding sites, termed coPARSE-lncRNAs. Using this method, the authors identified 570 human coPARSE-lncRNAs with predicted zebrafish homologs, many of which showed functional conservation. CRISPR-Cas12a knockout and rescue assays revealed that knocking out human coPARSE-lncRNAs led to cell proliferation defects, which were rescued by their zebrafish homologs. Conversely, knocking down coPARSE-lncRNAs in zebrafish embryos caused developmental delays that were rescued by human homologs. The study also verified that human, mouse, and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs, supporting their functional conservation. Overall, the research provides a comprehensive approach to studying the functional conservation of lncRNAs across vertebrates and highlights the importance of lncRNAs in regulating vertebrate physiology.The study introduces lncRNA Homology Explorer (lncHOME), a computational pipeline that identifies long noncoding RNAs (lncRNAs) with conserved genomic locations and patterns of RNA-binding protein (RBP) binding sites, termed coPARSE-lncRNAs. Using this method, the authors identified 570 human coPARSE-lncRNAs with predicted zebrafish homologs, many of which showed functional conservation. CRISPR-Cas12a knockout and rescue assays revealed that knocking out human coPARSE-lncRNAs led to cell proliferation defects, which were rescued by their zebrafish homologs. Conversely, knocking down coPARSE-lncRNAs in zebrafish embryos caused developmental delays that were rescued by human homologs. The study also verified that human, mouse, and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs, supporting their functional conservation. Overall, the research provides a comprehensive approach to studying the functional conservation of lncRNAs across vertebrates and highlights the importance of lncRNAs in regulating vertebrate physiology.