The gasdermin (GSDM) family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis. This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization, pyroptosis, and the follow-up inflammatory response, which are crucial self-defense mechanisms against irritants and infections. GSDMs have been implicated in a range of diseases including, but not limited to, sepsis, viral infections, and cancer, either through involvement in pyroptosis or independently of this process. The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases. Current strategies for inhibiting GSDMD primarily involve binding to GSDMD, blocking GSDMD cleavage or inhibiting GSDMD-N-terminal (NT) oligomerization, albeit with some off-target effects. In this review, we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis, elucidate the activation mechanisms of GSDMs, explore their associations with a range of diseases, and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

Gasdermin (GSDM) 家族作为焦亡的关键参与者，因其在免疫和疾病中的关键作用而受到广泛关注。这种最近表征的成孔效应蛋白在膜透化、细胞焦亡和后续炎症反应等协调过程中至关重要，这些过程是针对刺激物和感染的重要自卫机制。 GSDM 与一系列疾病有关，包括但不限于败血症、病毒感染和癌症，无论是通过参与细胞焦亡还是独立于该过程。 GSDM 介导的细胞焦亡的调节作为治疗各种疾病的一种有前途的治疗策略而得到认可。目前抑制 GSDMD 的策略主要涉及与 GSDMD 结合、阻断 GSDMD 裂解或抑制 GSDMD-N 末端 (NT) 寡聚化，尽管存在一些脱靶效应。在这篇综述中，我们深入研究了对 GSDM 和细胞焦亡之间相互作用的前沿理解，阐明了 GSDM 的激活机制，探讨了它们与一系列疾病的关联，并讨论了开发 GSDMD 抑制剂的最新进展和潜在策略。