Large non-coding RNAs (ncRNAs) play crucial regulatory roles in gene expression through modular interactions. This review summarizes recent findings on the functional diversity and mechanisms of these ncRNAs. The mammalian genome is extensively transcribed, producing thousands of non-coding transcripts, many of which are functional. Recent studies suggest that large ncRNAs achieve regulatory specificity through modularity, assembling diverse combinations of proteins and possibly RNA and DNA interactions. The discovery of ncRNAs, such as XIST and H19, has revealed their roles in gene regulation, including X-chromosome inactivation and imprinting. These ncRNAs often interact with chromatin regulatory complexes, influencing gene expression and chromatin structure. For example, XIST RNA interacts with the polycomb complex to silence the X chromosome, while HOTAIR regulates chromatin modifications and gene expression. The functional roles of ncRNAs are increasingly understood through global studies, including chromatin signatures and RNA sequencing. These studies have identified thousands of well-expressed large ncRNAs with cell-type and tissue specificity. However, the functional significance of many ncRNAs remains unclear, with some being considered transcriptional noise. The coding potential of ncRNAs is assessed through evolutionary conservation, homology to protein domains, and ribosome profiling. While some ncRNAs lack coding potential, others have distinct subclasses, including processed small RNAs and functional large ncRNAs. Functional studies have shown that many ncRNAs regulate gene expression through cis- and trans-regulatory mechanisms. For example, lincRNAs can act as cis-regulators by influencing neighboring genes on the same allele, while others function as trans-regulators by affecting genes across different alleles. RNA-protein interactions are a key aspect of ncRNA function, with many ncRNAs serving as molecular scaffolds for chromatin regulatory complexes. These interactions are essential for processes such as chromatin modification, transcriptional regulation, and gene silencing. The modular nature of ncRNAs is supported by their ability to form distinct RNA-protein interactions, which allow for precise regulatory functions. This modular code suggests that ncRNAs can be engineered to carry out specific regulatory roles in cells. Overall, large ncRNAs are essential for diverse biological processes, and their functional roles are increasingly being elucidated through genomic and functional studies. Understanding these mechanisms is crucial for advancing our knowledge of gene regulation and developing new therapeutic strategies.Large non-coding RNAs (ncRNAs) play crucial regulatory roles in gene expression through modular interactions. This review summarizes recent findings on the functional diversity and mechanisms of these ncRNAs. The mammalian genome is extensively transcribed, producing thousands of non-coding transcripts, many of which are functional. Recent studies suggest that large ncRNAs achieve regulatory specificity through modularity, assembling diverse combinations of proteins and possibly RNA and DNA interactions. The discovery of ncRNAs, such as XIST and H19, has revealed their roles in gene regulation, including X-chromosome inactivation and imprinting. These ncRNAs often interact with chromatin regulatory complexes, influencing gene expression and chromatin structure. For example, XIST RNA interacts with the polycomb complex to silence the X chromosome, while HOTAIR regulates chromatin modifications and gene expression. The functional roles of ncRNAs are increasingly understood through global studies, including chromatin signatures and RNA sequencing. These studies have identified thousands of well-expressed large ncRNAs with cell-type and tissue specificity. However, the functional significance of many ncRNAs remains unclear, with some being considered transcriptional noise. The coding potential of ncRNAs is assessed through evolutionary conservation, homology to protein domains, and ribosome profiling. While some ncRNAs lack coding potential, others have distinct subclasses, including processed small RNAs and functional large ncRNAs. Functional studies have shown that many ncRNAs regulate gene expression through cis- and trans-regulatory mechanisms. For example, lincRNAs can act as cis-regulators by influencing neighboring genes on the same allele, while others function as trans-regulators by affecting genes across different alleles. RNA-protein interactions are a key aspect of ncRNA function, with many ncRNAs serving as molecular scaffolds for chromatin regulatory complexes. These interactions are essential for processes such as chromatin modification, transcriptional regulation, and gene silencing. The modular nature of ncRNAs is supported by their ability to form distinct RNA-protein interactions, which allow for precise regulatory functions. This modular code suggests that ncRNAs can be engineered to carry out specific regulatory roles in cells. Overall, large ncRNAs are essential for diverse biological processes, and their functional roles are increasingly being elucidated through genomic and functional studies. Understanding these mechanisms is crucial for advancing our knowledge of gene regulation and developing new therapeutic strategies.