A major hurdle in contemporary medicine is the complicated and potentially fatal illness known as sepsis, which develops as a systemic inflammatory reaction to an infection [1]. Sepsis is a prominent cause of morbidity and mortality globally, characterized by a dysregulated host response that can result in tissue damage, extensive inflammation, and organ failure [2]. New findings have revealed pyroptosis as a key role in the pathophysiology of sepsis, which has further complicated our understanding of this illness [3]. At its core, sepsis represents the body's exaggerated and uncontrolled response to an infection, triggering a cascade of events that can have detrimental effects on vital organs [4]. The systemic inflammatory response associated with sepsis, if left unchecked, can result in organ damage and failure [5]. Pyroptosis, a distinctive form of targeted cell death, has recently taken the forefront in understanding this intricate interplay [6], [7]. Unlike apoptosis, pyroptosis induces an inflammatory response, releasing pro-inflammatory cytokines and other intracellular contents that amplify the immune response [8], [9]. The emerging recognition of pyroptosis as a significant contributor to sepsis-induced organ damage has ignited a fervor of research aimed at deciphering its molecular underpinnings [10].

In parallel with the growing understanding of sepsis and pyroptosis, the landscape of molecular biology has witnessed a transformative shift in our perception of ncRNAs [11]. Traditionally considered non-functional, these RNA molecules, devoid of protein-coding potential, are now recognized as essential regulators of cellular processes and gene expression [10], [12]. This class includes lncRNAs, miRNAs, and circRNAs, each with distinct roles in shaping the cellular landscape [13], [14]. While miRNAs are known for their post-transcriptional gene regulation, lncRNAs, with their varied functions, and circRNAs, a relatively newly discovered class, contribute to the intricate symphony of cellular activities [15]. The intersection of sepsis, pyroptosis, and ncRNAs unveils a fascinating regulatory network [16]. Current research has delved into the role of ncRNAs, particularly lncRNAs, in modulating the expression of key pyroptosis-related genes and proteins [17]. This regulatory influence extends to various stages of the pyroptotic process, from priming and activation to execution [18]. The intricate control exerted by ncRNAs on pyroptosis highlights their significance as molecular orchestrators in the complex landscape of septic pathogenesis [19]. As we navigate the specific implications of ncRNAs in sepsis-induced organ damage, a closer examination of lncRNAs reveals their intricate involvement in key organs [20]. Specific lncRNAs have been implicated in the regulation of pyroptosis in the context of sepsis-induced acute kidney injury, myocardial injury, and other organ damage [21]. These findings underscore the organ-specific nuances of ncRNA-mediated regulation, presenting a mosaic of molecular events that contribute to the diverse manifestations of septic organ dysfunction [22], [23]. Understanding the regulatory role of ncRNAs in pyroptosis opens new vistas for therapeutic interventions in sepsis [24], [25]. The potential significance lies not only in unraveling the molecular intricacies of septic pathogenesis but also in offering novel avenues for therapeutic strategies. The targeted manipulation of ncRNAs holds promise for mitigating the devastating effects of pyroptosis in sepsis, presenting a paradigm shift in our approach to this life-threatening condition (Fig. 1).