Glucose-induced degradation protein 8 homolog

GID8 (glucose-induced degradation protein 8 homolog) is a 228-amino acid component of the CTLH E3 ubiquitin-protein ligase complex (UniProt: Q9NWU2). It functions as a selective acceptor of ubiquitin from UBE2H, catalyzing proteasomal degradation of the transcription factor HBP1 and promoting Wnt signaling activation through beta-catenin nuclear accumulation (UniProt: Q9NWU2).

GID8 lacks reported monogenic disease associations in UniProt; however, its roles in ubiquitin-mediated protein degradation and Wnt pathway regulation implicate it in cellular processes relevant to neurodegenerative disease biology.

In Alzheimer's disease, GID8 is consistently downregulated in human post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change = −0.58; Chaparral AD proteomics). This reduction was observed across subcellular fractions in TMT-labeled quantitative mass spectrometry analysis, suggesting a potential disruption of proteasomal quality control or Wnt signaling in AD pathology.