Advances in RNA biology have reshaped current thinking about genome function, revealing that long non-coding RNAs (lncRNAs) are fundamental regulators of gene expression across human physiology. This volume provides a coherent, evidence-based synthesis of how lncRNAs influence molecular and cellular processes in health and disease, integrating insights from genomics, epigenetics, and molecular medicine. The opening chapters introduce the genomic organization of lncRNAs and the bioinformatic tools and databases that support their study, followed by detailed examinations of their mechanistic roles in stem cell biology, tissue regeneration, nutrient sensing, metabolic regulation, aging, and cellular senescence. Subsequent contributions explore how lncRNAs modulate pathways implicated in carcinogenesis, including diagnostic applications, therapeutic resistance, and the functional interplay between lncRNAs, chromatin remodeling, transcriptional regulation, and RNA–protein interactions. Additional chapters focus on disease-specific contexts, presenting current knowledge on lncRNA involvement in gastrointestinal, renal, bone, infectious, and rare diseases. Throughout these discussions, the volume emphasizes experimentally supported mechanisms and the biological significance of lncRNA-mediated regulatory networks. A dedicated translational perspective highlights the promise of lncRNAs as sensitive biomarkers detectable in biological fluids and exosomes, as well as their emerging potential as targets for precision medicine. By bringing together a broad range of established research areas in a structured, accessible format, the volume offers a comprehensive reference for readers in human genetics, molecular biology, clinical research, and bioinformatics seeking to understand the functional and therapeutic implications of long non-coding RNA biology.