The clinical phenotype of CEDS patients represented a paradox because<unk> -8 was considered to be chiefly a pro-apoptotic protease, that was mainly involved in signal transduction. The defect in lymphocyte activation and protective immunity suggested that<unk> -8 had additional signaling roles in lymphocytes. Further work revealed that<unk> -8 was essential for the induction of the transcription factor “nuclear factor κB” (NF-κB) after stimulation through antigen receptors, Fc receptors, or Toll-like receptor 4 in T, B, and natural killer cells. Biochemically,<unk> -8 was found to enter the complex of the inhibitor of NF-κB kinase (IKK) with the upstream Bcl10-MALT1 (mucosa-associated lymphatic tissue) adapter complex which were crucial for the induction of nuclear translocation of NF-κB. Moreover, the biochemical form of<unk> -8 differed in the two pathways. For the death pathway, the<unk> -8 zymogen is cleaved into subunits that assemble to form the mature, highly active<unk>  heterotetramer whereas for the activation pathway, the zymogen appears to remain intact perhaps to limit its proteolytic function but enhance its capability as an adapter protein.
Caspase-8 deficiency
Janus kinase 3 deficiency
ZAP70 deficiency
NGLY1 deficiency
LRBA deficiency
Leukocyte adhesion molecule deficiency
CDKL5 deficiency disorder
PMM2 deficiency