Ribonuclease inhibitor

Ribonuclease inhibitor (RNH1) is a 461-amino acid cytoplasmic protein that suppresses the ribonucleolytic activity of RNASE1, RNASE2, and angiogenin (ANG) (UniProt: P13489). The protein plays dual roles in redox homeostasis and stress-responsive nuclear translocation; under normal conditions it inhibits ANG's cytotoxic tRNA cleavage activity in the cytoplasm, but upon cellular stress it relocates to the nucleus to modulate ANG's angiogenic function (UniProt: P13489). A rare autosomal recessive disorder (acute infection-induced encephalitis, IIAE12) has been associated with RNH1 mutations, presenting with seizures and neurologic complications triggered by viral infections.

In Alzheimer's disease, RNH1 shows ambiguous regulation across subcellular fractions in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.22 (Chaparral AD proteomics). This modest and inconsistent directionality across the four fractions examined (P2, P3, S2, S3) suggests either marginal dysregulation or compartment-specific changes that do not uniformly indicate upregulation or downregulation in AD pathology.