PIWI-Interacting RNAs: Biogenesis, Molecular Mechanisms, Computational Advances, and Roles in Human Health and Disease.

PIWI-associated RNAs (piRNAs) are a diverse and abundant class of small regulatory non-coding RNAs that play central roles in genome regulation and transposon silencing. First identified in germline cells, piRNAs are now also implicated in somatic cell function, stem cell maintenance, immunity, and human disease, particularly cancer and neurodegeneration. This review follows the evolution of piRNA research, highlighting advances in their biogenesis, molecular mechanisms, and multifaceted roles in gene regulation. It also outlines how recent computational developments, especially deep learning and network-based models, together with dedicated databases and web tools, have improved functional and disease-association prediction, and discusses emerging clinical applications of piRNAs as diagnostic biomarkers and therapeutic targets at the frontiers of RNA-based precision medicine.