GET4 (Golgi to ER traffic protein 4 homolog) Summary

GET4 is a 36.5 kDa cytosolic protein that functions as a component of the BAG6/BAT3 protein quality control complex (UniProt: Q7L5D6). This complex maintains misfolded and hydrophobic proteins in a soluble state and directs them either to the endoplasmic reticulum for proper localization or to the proteasome for degradation. GET4 participates specifically in post-translational delivery of tail-anchored proteins to the ER membrane and in ER-associated degradation (ERAD), a cellular mechanism for eliminating unwanted ER proteins.

GET4 is associated with congenital disorder of glycosylation type 2Y (CDG2Y; MIM 620200), an autosomal recessive condition characterized by developmental delay, hypotonia, seizures, and brain abnormalities (UniProt: Q7L5D6). The protein's role in protein trafficking and quality control suggests relevance to cellular proteostasis pathways that maintain proper protein folding and localization in the secretory pathway.

In Alzheimer's disease, GET4 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.48 across analyzed subcellular fractions. This reduced expression may reflect impaired protein quality control mechanisms in AD neurodegeneration.