CASP8是抑癌基因，编码蛋白为半胱氨酸-天冬氨酸蛋白酶（Caspase）家族的一位成员。CASP8蛋白是调节诱导凋亡的死亡受体的主要起始Caspase。与细胞凋亡相关的CD95（Fas / Apo1），肿瘤坏死因子（TNF），以及（TRAIL）受体和TNF受体通过形成诱导死亡的信号复合物（DISC）参与激活信号级联反应，最终导致CASP8的蛋白水解活化。激活后，CASP8可以直接切割其他半胱天冬酶，例如胱天蛋白酶-3，或通过切割BID（BH3-相互作用结构域死亡激动剂）来参与线粒体途径。另外，CASP8参与介导抗凋亡NF-κB途径和抑制受体相互作用蛋白激酶-3（RIPK3）依赖性坏死样凋亡。已经在神经母细胞瘤和肺癌细胞系中鉴定了CASP8的其他非蛋白水解功能，包括促进细胞粘附，运动性和转移。在肝癌、胃癌、结直肠癌、中枢神经系统恶性肿瘤和头颈部癌在内的不同癌症中已经观察到各种失活的体细胞突变以及通过启动子高甲基化引起的CASP8基因沉默。Caspase-8 deficiency state（CEDS）是一种由CASP8突变引起的罕见的遗传性疾病，类似于自身免疫性淋巴增生综合征（ALPS）。

The CASP8 gene encodes a member of the cysteine-aspartic acid protease (caspase) family. The CASP8 protein is the main initiator caspase that mediates death receptor-induced apoptosis. CD95 (Fas/Apo1), tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors and TNF receptors are involved in activating the signaling cascade through formation of a death-inducing signaling complex (DISC), which ultimately leads to proteolytic activation of CASP8. Upon activation, CASP8 can directly cleave other caspases, such as caspase-3, or engage the mitochondrial pathway by cleavage of BID (BH3-interacting domain death agonist). Additionally, CASP8 is involved in mediating the anti-apoptotic NF-κB pathway and inhibiting receptor interacting protein kinase-3 (RIPK3)-dependent necroptosis. Other non-proteolytic functions of CASP8 have been identified in neuroblastoma and lung cancer cell lines including promotion of cell adhesion, motility and metastasis. Various inactivating somatic mutations as well as gene silencing by promoter hypermethylation of CASP8 have been observed in different cancers including hepatocellular, gastric, colorectal, central nervous system malignancies and head and neck cancers. Caspase-8 deficiency state (CEDS) is a rare genetic disorder that is caused by CASP8 mutations and resembles autoimmune lymphoproliferative syndrome (ALPS).

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