Small ribosomal subunit protein uS3

Small ribosomal subunit protein uS3 (RPS3) is a 243-amino acid component of the small ribosomal subunit that functions in protein synthesis (UniProt: P23396). Beyond its canonical ribosomal role, RPS3 has DNA repair and damage-sensing functions, binding 8-oxoguanine lesions and stimulating base excision repair enzymes OGG1 and UNG1. It also participates in transcriptional regulation via the NF-κB complex, apoptosis regulation through p53 protection and caspase-8 activation, and mitotic spindle organization.

RPS3 is broadly expressed and has been implicated in cellular stress responses. UniProt lists no curated disease associations in its primary record (UniProt: P23396), though its roles in DNA repair and apoptosis are relevant to neurodegenerative processes.

In Alzheimer's disease, RPS3 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.33; Chaparral AD proteomics). This downregulation was observed across 4 subcellular fractions in TMT-labeled proteomic analysis, suggesting reduced levels of this multifunctional protein in the AD brain may compromise ribosomal function and stress-response capacity.