近年来，我们对调控细胞死亡的认识不断扩展，从而发现了管理多样化细胞死亡途径的新机制。最近发现的一种细胞死亡类型是热凋亡，最初在1990年代被确认为依赖caspase-1的溶解性细胞死亡。然而，进一步研究已将热凋亡重新定义为一种依赖于孔形成蛋白特别是gasdermin家族活化的调控细胞死亡方式。热凋亡的主要调控因子之一是炎症小体传感器NOD样受体3（NLRP3），它是一种关键的先天免疫传感器，负责调控caspase-1和gasdermin D的活化。对热凋亡及其与其他形式调控细胞死亡之间相互作用的更深入理解正在涌现，揭示了控制孔形成蛋白和细胞命运的复杂调控网络。细胞死亡过程在代谢功能障碍相关脂肪肝病、代谢功能障碍相关脂肪肝炎、自身炎症性疾病和癌症等疾病中起着核心作用。细胞死亡往往是这些疾病的起始点，使其成为药物开发的有吸引力的靶点。然而，完整的分子机制尚未完全理解，新的发现揭示了治疗干预的有希望的新途径。在本综述中，我们总结了关于调控热凋亡和孔形成蛋白的途径和蛋白的最新证据。此外，我们还将讨论热凋亡和gasdermin家族在代谢功能障碍相关脂肪肝病和脂肪肝炎中的作用。此外，我们还强调了治疗代谢功能障碍相关脂肪肝炎和其他炎症相关疾病的新潜在治疗靶点。 Copyright© 2023 Stoess, Leszczynska, Kui and Feldstein.

In recent years, there has been a rapid expansion in our understanding of regulated cell death, leading to the discovery of novel mechanisms that govern diverse cell death pathways. One recently discovered type of cell death is pyroptosis, initially identified in the 1990s as a caspase-1-dependent lytic cell death. However, further investigations have redefined pyroptosis as a regulated cell death that relies on the activation of pore-forming proteins, particularly the gasdermin family. Among the key regulators of pyroptosis is the inflammasome sensor NOD-like receptor 3 (NLRP3), a critical innate immune sensor responsible for regulating the activation of caspase-1 and gasdermin D. A deeper understanding of pyroptosis and its interplay with other forms of regulated cell death is emerging, shedding light on a complex regulatory network controlling pore-forming proteins and cell fate. Cell death processes play a central role in diseases such as metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, autoinflammatory disorders, and cancer. Cell death often acts as a starting point in these diseases, making it an appealing target for drug development. Yet, the complete molecular mechanisms are not fully understood, and new discoveries reveal promising novel avenues for therapeutic interventions. In this review, we summarize recent evidence on pathways and proteins controlling pyroptosis and gasdermins. Furthermore, we will address the role of pyroptosis and the gasdermin family in metabolic dysfunction-associated steatotic liver disease and steatohepatitis. Additionally, we highlight new potential therapeutic targets for treating metabolic dysfunction-associated steatohepatitis and other inflammatory-associated diseases.Copyright © 2023 Stoess, Leszczynska, Kui and Feldstein.