RNF10 is an E3 ubiquitin ligase that functions as a critical component of ribosome quality control, catalyzing monoubiquitination of 40S ribosomal proteins RPS2 and RPS3 in response to translation stress 12. RNF10 operates within two distinct quality control pathways: initiation-stage ribosome quality control (iRQC) and elongation-stage mechanisms, both activated by ribosomal subunit imbalance, amino acid starvation, or the integrated stress response downstream of GCN2 345. Mechanistically, RNF10-mediated monoubiquitination marks dysfunctional 40S subunits for recognition by RIOK3 kinase, triggering 18S non-functional rRNA decay and selective 40S ribosomal subunit degradation 46. RNF10 activity is counteracted by the deubiquitinase USP10, providing regulatory balance 2. RNF10 expression levels are tightly coupled to 40S subunit abundance, with protein degradation occurring under 40S biogenesis disruption and accumulation under 60S biogenesis impairment, establishing RNF10 as a sensor of ribosomal stoichiometry 3. Beyond ribosomal function, RNF10 serves as a synaptonuclear messenger regulating synaptic plasticity and transcription 7, and dysregulation of RNF10 expression is associated with aging-related immune dysfunction 8.