SECISBP2 (SECIS binding protein 2) is an mRNA-binding protein that facilitates selenocysteine (Sec) incorporation into selenoproteins by binding the SECIS element in the 3'-UTR of selenoprotein-encoding mRNAs 1. The protein specifically recognizes the SECIS sequence when the 80S ribosome encounters an in-frame UGA codon and contacts the 40S ribosomal protein eS31, enabling the Sec-specific elongation factor EEFSEC to deliver selenocysteinyl-tRNA(Sec) 1. Beyond its canonical role in translation recoding, SECISBP2 also stabilizes selenoprotein mRNAs through gene-specific mechanisms 2. Loss of SECISBP2 function results in systemic selenoprotein deficiency with multifactorial clinical consequences. Patients with SECISBP2 mutations develop early-onset aortic aneurysms through oxidative stress and vascular smooth muscle cell apoptosis 3, thyroid hormone metabolism defects due to reduced deiodinase expression 4, myopathy, photosensitivity, and hearing loss 5. In diffuse large B-cell lymphoma, elevated SECISBP2 expression correlates with poor prognosis and promotes chemotherapy resistance through enhanced GPX4 and TXNRD1 selenoprotein synthesis 6. SECISBP2 represents both a critical mediator of selenoprotein homeostasis and a potential therapeutic target in cancer and oxidative stress-related diseases 7.