<p>Long non-coding RNAs (lncRNAs) have emerged as critical regulators of kidney homeostasis, and their dysregulation has been implicated in a wide range of kidney diseases including acute kidney injury, chronic kidney disease and renal cell carcinoma, as well as in age-related kidney dysfunction. Increasing evidence indicates that lncRNAs have roles in key cellular processes including inflammation, autophagy, cell proliferation, senescence, apoptosis, mitochondrial dysfunction, angiogenesis, epithelial–mesenchymal transition and interstitial fibrosis. LncRNAs interact with RNA, DNA and protein to regulate gene expression via multiple mechanisms, including RNA modifications, scaffold assembly, chromatin remodelling, transcription and post-transcriptional control. Beyond their non-coding functions, some lncRNAs can be translated into bioactive micropeptides that further modulate cellular activity. Given their tissue-specific expression and high stability in body fluids, lncRNAs hold promise as biomarkers for early detection and monitoring of kidney diseases. Furthermore, lncRNA-based therapies offer novel opportunities to halt disease progression in chronic kidney disease and overcome drug resistance in renal cell carcinoma. Improved understanding of lncRNA-mediated disease mechanisms could therefore lead to improvements in the diagnosis and treatment of kidney pathologies.</p>