{Reference Type}: Journal Article {Title}: Plumbing mysterious RNAs in "dark genome" for the conquest of human diseases. {Author}: Huang LA;Lin C;Yang L; {Journal}: Mol Ther {Volume}: 31 {Issue}: 6 {Year}: 2023 06 7 {Factor}: 12.91 {DOI}: 10.1016/j.ymthe.2023.05.003 {Abstract}: Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion transcribed into noncoding RNAs (ncRNAs). Among these, long noncoding RNAs (lncRNAs) represent the largest group and are pervasively transcribed throughout the genome. Dysfunctions in lncRNAs have been found in various diseases, highlighting their potential as therapeutic, diagnostic, and prognostic targets. However, challenges, such as unknown molecular mechanisms and nonspecific immune responses, and issues of drug specificity and delivery present obstacles in translating lncRNAs into clinical applications. In this review, we summarize recent publications that have explored lncRNA functions in human diseases. We also discuss challenges and future directions for developing lncRNA treatments, aiming to bridge the gap between functional studies and clinical potential and inspire further exploration in the field.