Termed ‘master gene regulators’ long ncRNAs (lncRNAs) have emerged as the true vanguard of the ‘noncoding revolution’. Functioning at a molecular level, in most if not all cellular processes, lncRNAs exert their effects systemically. Thus, it is not surprising that lncRNAs have emerged as important players in human pathophysiology. As our body's first line of defense upon infection or injury, inflammation has been implicated in the etiology of several human diseases. At the center of the acute inflammatory response, as well as several pathologies, is the pleiotropic transcription factor NF-κβ. In this review, we attempt to capture a summary of lncRNAs directly involved in regulating innate immunity at various arms of the NF-κβ pathway that have also been validated in human disease. We also highlight the fundamental concepts required as lncRNAs enter a new era of diagnostic and therapeutic significance.

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