Triokinase/FMN cyclase (TKFC) Summary

TKFC is a bifunctional enzyme that catalyzes phosphorylation of dihydroxyacetone and glyceraldehyde, and processes ribonucleoside diphosphate compounds, with FAD as its preferred substrate (UniProt: Q3LXA3). The protein also represses IFIH1-mediated antiviral responses, linking it to innate immunity regulation.

Biallelic mutations in TKFC cause triokinase and FMN cyclase deficiency syndrome, an autosomal recessive condition presenting with cataracts, developmental delay, and potentially cerebellar hypoplasia, liver dysfunction, microcytic anemia, and fatal cardiomyopathy (UniProt: Q3LXA3, MIM 618805). These manifestations suggest a role in metabolic homeostasis, particularly flavin metabolism.

TKFC is significantly upregulated in post-mortem Alzheimer's Disease brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log₂FC of +0.99 measured across subcellular fractions by TMT-labeled quantitative proteomics. This elevation may reflect altered riboflavin metabolism or heightened antiviral-immune signaling in the AD brain microenvironment, though the mechanistic link to neurodegeneration remains to be determined.