embryonic lethal due to liver apoptosis. Lymphocyte activation failure is also observed, suggesting that RELA is indispensable in the proper development of the immune system. In comparison, deletion of other REL-related genes will not cause embryonic development failure, though different levels of defects are also noted. The fact that cytokines such as TNFα and IL-1 can stimulate the activation of RELA also supports its participation in immune response. In general, RELA participates in adaptive immunity and responses to invading pathogens via NF-κB activation. Mice without individual NF-κB proteins are deficient in B- and T-cell activation and proliferation, cytokine production and isotype switching. Mutations in RELA is found responsible for inflammatory bowel disease as well. Cancer NF-κB/RELA activation has been found to be correlated with cancer development, suggesting the potential of RELA as a cancer biomarker. Specific modification patterns of RELA have also been observed in many cancer types. Prostate RELA may have a potential role as biomarker for prostate cancer progression and metastases, as suggested by the association found between RELA nuclear localization and prostate cancer aggressiveness and biochemical recurrence. Thyroid Strong correlation between nuclear localization of RELA and clinicopathological parameters for papillary thyroid carcinoma (PTC), suggesting the role of NF-κB activation in tumor growth and aggressiveness in PTC. Other than usage as an biomarker, serine 536 phosphorylation in RELA is also correlated with nuclear translocation and the expression of some transactivating genes such as COX-2, IL-8 and GST-pi in follicular thyroid carcinomas via morphoproteomic analysis. Leukemia Mutations in the transactivation domain of RELA can lead to decrease in transactivating ability and this mutation can be found in lymphoid neoplasia. Head and Neck Nuclear localization of NF-κB/RELA is positively correlated with tumor micrometastases into lymph and blood and negatively correlated with patient survival outcome in patients with head and neck squamous cell carcinoma (HNSCC). This suggests a role of NF-κB/RELA as a possible target for targeted-therapy. Breast There is both a physical and a functional association between RELA and aryl hydrocarbon receptor (AhR), and the subsequent activation of c-myc gene transcription in breast cancer cells. Another paper reported interactions between estrogen receptor (ER) and NF-κB members, including p50 and RELA. It is shown that ERα interacts with both p50 and RELA in vitro and in vivo, and RELA antibody can reduce ERα:ERE complex formation. The paper claims a mutual repression between ER and NF-κB. Monogenic Behçet’s Disease-like conditions Behçet's disease-like