A computational pipeline called lncHOME was developed to identify long noncoding RNAs (lncRNAs) with conserved genomic locations and RNA-binding protein (RBP) binding site patterns across species, termed coPARSE-lncRNAs. The study identified 570 human coPARSE-lncRNAs with predicted zebrafish homologs, of which only 17 showed detectable sequence similarity. Functional studies using 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. Similarly, knocking down coPARSE-lncRNAs in zebrafish embryos caused developmental delays that were rescued by human homologs. The study also showed that human, mouse, and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs, indicating functional conservation. The research highlights the importance of conserved RBP-binding sites in lncRNA function and provides a framework for studying functional conservation of lncRNAs across vertebrates. The study demonstrates that coPARSE-lncRNAs play significant roles in regulating vertebrate physiology, with several identified as being involved in cancer progression. The findings suggest that lncRNAs may have conserved functions despite limited sequence conservation, and that their functional conservation can be studied through their interactions with RBPs. The study also provides a powerful tool for further research on the functional conservation of lncRNAs.A computational pipeline called lncHOME was developed to identify long noncoding RNAs (lncRNAs) with conserved genomic locations and RNA-binding protein (RBP) binding site patterns across species, termed coPARSE-lncRNAs. The study identified 570 human coPARSE-lncRNAs with predicted zebrafish homologs, of which only 17 showed detectable sequence similarity. Functional studies using 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. Similarly, knocking down coPARSE-lncRNAs in zebrafish embryos caused developmental delays that were rescued by human homologs. The study also showed that human, mouse, and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs, indicating functional conservation. The research highlights the importance of conserved RBP-binding sites in lncRNA function and provides a framework for studying functional conservation of lncRNAs across vertebrates. The study demonstrates that coPARSE-lncRNAs play significant roles in regulating vertebrate physiology, with several identified as being involved in cancer progression. The findings suggest that lncRNAs may have conserved functions despite limited sequence conservation, and that their functional conservation can be studied through their interactions with RBPs. The study also provides a powerful tool for further research on the functional conservation of lncRNAs.