LENG8 (leukocyte receptor cluster member 8) is a conserved nuclear protein that functions as a critical regulator of RNA quality control and mRNA export. Primary function: LENG8 mediates nuclear retention and degradation of misprocessed and noncoding RNAs 12. Mechanism: LENG8 is recruited to pre-mRNAs by splicing factors including U1 snRNP and associates with PCID2 and SEM1 to form the REX (repressor of export) complex 12. This complex acts as a dominant-negative inhibitor of the essential mRNA export factor TREX-2, preventing aberrant RNA export 12. LENG8 also promotes nuclear RNA degradation by recruiting the RNA exosome adaptor PAXT 12. LENG8 additionally functions within TREX-2.1 complex, where its trigger loop regulates the DEAD-box ATPase DDX39B to influence nucleocytoplasmic distribution of GC-rich mRNAs 3. Disease relevance: LENG8 has been implicated in multiple disease contexts. Homozygous deleterious variants in LENG8 were identified in patients with compatible Mendelian phenotypes 4. A LENG8 antisense RNA (LENG8-AS1) was identified as a prognostic biomarker in colorectal cancer 5, and LENG8 was identified as a hub gene in obesity-associated osteoarthritis 6. Clinical significance: LENG8's role in ensuring only correctly processed RNAs are exported provides a fundamental quality-control mechanism for eukaryotic gene expression, with therapeutic implications for cancers and genetic disorders.