Tradd, short for Tumor Necrosis Factor Receptor Type 1-Associated Death Domain Protein, is an adaptor protein. It is involved in various signal pathways, mediating multiple biological activities such as cell survival, proliferation, differentiation, apoptosis, necroptosis, and inflammation [2]. After specific receptor activation like TNFR1, it binds to receptors, acting as a platform for downstream molecule recruitment to propagate signals.

In KO mouse models, combined RIPK1 inhibition and Tradd knockout protected against intestinal pathology and lethality in TAK1 IEC KO mice, revealing the cooperation between RIPK1 and Tradd in mediating cell death and inflammation in inflammatory bowel disease (IBD) [3]. In Ripk1 -/-Ripk3 -/- mice, ablation of Tradd rescued them from perinatal lethality, with Tradd playing a crucial role in perinatal and adult mice lacking RIPK1 and RIPK3 [4]. Also, in a mouse model of proteinopathy induced by mutant tau(P301S), treatment with Apt-1 (which inhibits Tradd) restored proteostasis and inhibited cell death [1].

In conclusion, Tradd is a key player in multiple biological processes related to cell survival and death. Studies using KO mouse models have demonstrated its significance in diseases like IBD and proteinopathy, highlighting its potential as a therapeutic target for these conditions.