TNF receptor-associated factor 5

TRAF5 (TNF receptor-associated factor 5) is an adapter protein and signal transducer that mediates signaling downstream of tumor necrosis factor receptors by binding to receptor cytoplasmic domains and recruiting kinases. It functions to activate NF-κB and JNK pathways and is implicated in apoptosis regulation and PKR-dependent signaling (UniProt: O00463).

TRAF5 is broadly expressed across tissues and participates in inflammatory and cell-death signaling networks. No baseline disease associations are documented in UniProt for this protein.

In Alzheimer's disease, TRAF5 shows consistent downregulation in post-mortem AD brain relative to age-matched controls (Chaparral AD proteomics). The protein was decreased with a mean log2 fold-change of −0.58 across subcellular fractions in TMT-labeled quantitative mass spectrometry analysis. This reduction may reflect altered TNF signaling or impaired NF-κB activation in the AD brain milieu.