SERBP1 (SERPINE1 mRNA-binding protein 1) is a multifunctional RNA-binding protein that operates primarily through ribosome regulation and mRNA stability control. Its primary function involves promoting ribosome hibernation by associating with the translation elongation factor EEF2, sequestering it at the ribosomal A-site to stabilize ribosomes in an inactive, storage-competent state 1. SERBP1 also regulates mRNA stability by binding to the 3'-UTR of SERPINE1 mRNA, modulating cyclic nucleotide-dependent decay 2, and participates in PML-nuclear body organization 3. Mechanistically, SERBP1 functions as a dynamic regulator through intrinsically disordered regions, interacting with PARP1 and participating in PARylation-dependent complexes that regulate splicing, cell division, and ribosomal biogenesis 4. It negatively regulates the ribotoxic stress response by inhibiting ZAK activation at collided ribosomes 5. Clinically relevant disease associations include glioblastoma, where HERC5/ISG15-mediated SERBP1 stabilization promotes tumor stemness and progression 6; diabetic complications, where Adipsin-SERBP1 interactions regulate SERPINE1 expression affecting angiogenesis 7; breast cancer tumorigenicity through RCC2-lactylation-mediated SERBP1 recruitment 8; and KSHV-associated cancers through ferroptosis regulation 9. SERBP1 represents an emerging therapeutic target across multiple malignancies and metabolic diseases.