Glutaredoxin-3

Glutaredoxin-3 (GLRX3) is a cytosolic iron-sulfur cluster assembly factor that works in conjunction with BOLA2 to facilitate [2Fe-2S] cluster insertion into a subset of cytosolic proteins (UniProt: O76003). The protein also functions as a critical negative regulator of cardiac hypertrophy and is required for hemoglobin maturation, though it lacks thyoredoxin catalytic activity.

GLRX3 is predominantly expressed in cytosolic compartments where it participates in iron-sulfur cluster biogenesis, a pathway essential for the maturation of metalloproteins involved in energy metabolism and redox homeostasis (UniProt: O76003). No specific tissue disease associations are currently documented in UniProt curated records.

In Alzheimer's disease, GLRX3 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.18 (Chaparral AD proteomics). This modest upregulation suggests a potential compensatory response to altered iron-sulfur cluster metabolism or oxidative stress associated with neurodegeneration. The finding was derived from TMT-labeled quantitative proteomics across multiple subcellular fractions, indicating consistent elevation in AD neuropathology.