RPS25 (Ribosomal Protein S25) is a component of the small 40S ribosomal subunit involved in protein translation. The protein is encoded by the RPS25 gene located on chromosome 19q13.42 and is highly conserved across eukaryotes 1. RPS25 is a member of the S25e family of ribosomal proteins and plays critical roles in ribosome assembly, translation initiation, and mRNA binding 1.
| RPS25 Protein | |
|---|---|
| Protein Name | Ribosomal Protein S25 |
| Gene | [RPS25](/genes/rps25) |
| UniProt | [P62875](https://www.uniprot.org/uniprot/P62875) |
| Location | Cytoplasm, ribosome |
| Function | Protein translation |
| MW | 13.7 kDa |
RPS25 contains an N-terminal domain involved in rRNA binding and a C-terminal domain that contacts the mRNA channel 1. The protein interfaces with 18S rRNA and ribosomal proteins S3, S10, and S14.
RPS25 contributes to 40S subunit assembly and maturation, initiation complex formation, and association with eukaryotic initiation factors (eIFs) 1.
RPS25 and other ribosomal proteins are affected in AD through ribosomal dysfunction and reduced protein synthesis capability in AD brains 2. Global translation deficits correlate with cognitive decline, and amyloid-beta causes ribosomal pausing and stress 3.
In PD, RPS25 is relevant through protein homeostasis disruption, where impaired translation affects alpha-synuclein clearance, and ER stress contributes to unfolded protein response 5.
Ribosomal protein dysregulation is observed in ALS/FTD, where TDP-43 pathology affects translation regulation, C9orf72 repeat expansions impact nucleolar stress, and global translation deficits occur in motor neurons 2.
The integrated stress response (ISR) plays a key role in neurodegenerative diseases. eIF2α phosphorylation causes global translation inhibition, while some mRNAs escape this shutdown through selective translation. Compensatory mechanisms targeting translation are being explored for neuroprotection 5.
Understanding ribosomal function in neurodegeneration offers several therapeutic approaches: translation modulators like eIF2α phosphorylation inhibitors, ribosome enhancers to improve translational capacity, and mTOR inhibitors such as rapamycin for autophagy induction 5.