Ribonuclease T2

Ribonuclease T2 (RNASET2) is a ribonuclease that degrades single-stranded RNA molecules preferentially between purine and uridine residues (UniProt: O00584). The enzyme plays a dual role in innate immunity and organellar homeostasis: it processes pathogenic microbial RNAs to generate ligands that activate toll-like receptors (TLR7 and TLR8), and it degrades mitochondrial RNA and processes non-coding RNAs imported into mitochondria (UniProt: O00584). Loss-of-function mutations cause leukoencephalopathy with cystic white matter lesions, seizures, and hearing impairment (LCWM, MIM 612951).

In Alzheimer's disease, RNASET2 is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein showed a mean log2 fold-change of +0.44 across subcellular fractions in TMT-labeled quantitative proteomics analysis of human post-mortem AD brain versus controls. This upregulation suggests potential involvement in neuroinflammatory and/or mitochondrial dysfunction pathways implicated in AD pathogenesis, though the functional consequences remain to be elucidated.