Casp8, also known as caspase-8, apoptosis-related cysteine peptidase, is an essential enzyme in the apoptosis pathway [6]. It plays a crucial role in regulating cell death and inflammation, which are fundamental biological processes [1]. Genetic models, such as KO/CKO mouse models, are valuable for studying Casp8's functions.

In various diseases, Casp8 shows diverse associations. In melanoma, TNFα and IFNγ synergistically upregulate Casp8 through IRF1 and ELAVL1, leading to cancer cell death, and high expression of Casp8 in tumors is related to better response to immune checkpoint blockade therapy [1]. In traumatic brain injury, Casp8 is identified as a potential therapeutic target correlated with pyroptosis [2]. In neuroblastoma, methylation of Casp8 is associated with poor prognosis, and low expression of Casp8 could be a prognostic biomarker [3,7]. In prostate cancer, high levels of Casp8 may serve as a biomarker for high-risk cases [5]. Prenatal exposure to polycyclic aromatic hydrocarbons can lead to Casp8 hypomethylation, which is associated with neural tube defects [4]. Also, Casp8 polymorphisms are related to cancer susceptibility, with some polymorphisms reducing and some increasing the risk [6].

In conclusion, Casp8 is a key regulator in cell death and inflammation. Studies using genetic models have revealed its significance in multiple disease areas, including cancer, traumatic brain injury, and neural tube defects. Understanding Casp8's functions and its associations with diseases provides valuable insights for tumor immunotherapy, individualized therapy for traumatic brain injury, and prevention of neural tube defects.