Dysregulated TNFR signalling is associated with many inflammatory disorders, including some forms of arthritis and inflammatory bowel disease, and targeting TNF has been an effective therapeutic strategy in these diseases and for cancer immunotherapy [1-2,5].

TNFRSF1A is preferentially activated by the shed form of TNF ligand, whereas the membrane-bound form of TNF serves to activate TNFRSF1A and TNFRSF1B equally. The neurotrophins nerve growth factor (NGF (NGF, P01138)), brain-derived neurotrophic factor (BDNF (BDNF, P23560)), neurotrophin-3 (NTF3, P20783) (NTF3) and neurotrophin-4 (NTF4, P34130) (NTF4) are structurally unrelated to the TNF ligand superfamily but exert some of their actions through the “low affinity nerve growth factor receptor” (NGFR (TNFRSF16)) as well as through the TRK family of receptor tyrosine kinases. The endogenous ligands for EDAR and EDA2R are, respectively, the membrane (Q92838[1-391]) and secreted (Q92838[160-391]) isoforms of Ectodysplasin-A (EDA, Q92838).

* Key recommended reading is highlighted with an asterisk

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David MacEwan Department of Pharmacology and Therapeutics Institute of Systems, Molecular and Integrative Biology University of Liverpool Liverpool, UK