SSB (La protein) is an RNA-binding protein that protects nascent RNA polymerase III transcripts, particularly tRNAs, from exonuclease degradation by binding their 3' poly(U) termini and facilitating their maturation and export. Beyond canonical RNA protection, SSB has emerged as a multifunctional regulator in cellular stress responses and disease. Recent evidence reveals that SSB cooperates with METTL16 to install m6A methylation on target RNAs, including SSB itself, creating a positive autoregulatory loop that enhances chemoresistance in colorectal cancer cells 1. SSB also participates in viral translation: during Coxsackievirus B3 infection, it binds to the viral internal ribosome entry site and stimulates IRES-mediated translation. The protein localizes to both the nucleus and cytoplasm, where it associates with stress granules and participates in tRNA processing, modification, and nuclear export. SSB has been implicated in multiple disease contexts including cancer (particularly hepatocellular carcinoma and lung cancer), lysosomal storage disorders, and as a target of autoimmune responses in systemic lupus erythematosus, where maternal anti-SSB/La antibodies are associated with congenital heart block. These diverse roles position SSB as a potential therapeutic target, particularly the METTL16/SSB axis in METTL16-dependent cancers such as colorectal cancer.