This study presents a comprehensive atlas of human long non-coding RNAs (lncRNAs) with accurate 5′ ends and expression profiles across various cell types and tissues. The authors integrated multiple transcript collections, including FANTOM5 cap analysis of gene expression (CAGE) data, to generate an atlas of 27,919 lncRNA genes. They found that most intergenic lncRNAs originate from enhancers rather than promoters. By integrating genetic and expression data, they identified lncRNAs overlapping trait-associated single nucleotide polymorphisms (SNPs) and expression quantitative trait loci (eQTL)-associated SNPs, suggesting their potential roles in disease and transcriptional regulation. The study also revealed that lncRNAs with conserved exons and transcription initiation regions (TIRs) are more likely to be functional. The authors concluded that 69% of the identified lncRNAs are potentially functional, advancing the understanding of pervasive transcription in mammalian genomes.This study presents a comprehensive atlas of human long non-coding RNAs (lncRNAs) with accurate 5′ ends and expression profiles across various cell types and tissues. The authors integrated multiple transcript collections, including FANTOM5 cap analysis of gene expression (CAGE) data, to generate an atlas of 27,919 lncRNA genes. They found that most intergenic lncRNAs originate from enhancers rather than promoters. By integrating genetic and expression data, they identified lncRNAs overlapping trait-associated single nucleotide polymorphisms (SNPs) and expression quantitative trait loci (eQTL)-associated SNPs, suggesting their potential roles in disease and transcriptional regulation. The study also revealed that lncRNAs with conserved exons and transcription initiation regions (TIRs) are more likely to be functional. The authors concluded that 69% of the identified lncRNAs are potentially functional, advancing the understanding of pervasive transcription in mammalian genomes.