RMND5A is a core component of the CTLH E3 ubiquitin-protein ligase complex that mediates selective ubiquitination and proteasomal degradation of target proteins 1. As a RING domain protein, RMND5A works with MAEA to catalyze K48 and K63 poly-ubiquitin chain formation, with both subunits interdependent for complex stability and activity 2. The CTLH complex catalytic activity is essential for normal cell proliferation 1. Beyond its classical E3 ligase function, RMND5A maintains self-renewal of human neural stem/precursor cells by suppressing Wnt signaling and activating mTOR pathways, contributing to cortical expansion during brain development 3. In endothelial cells, RMND5A overexpression inhibits proliferation, migration, and angiogenesis via ERK and NF-κB pathway suppression; conversely, oral cancer cells evade this through exosomal miR-21-mediated RMND5A downregulation 4. Clinically, RMND5A dysregulation associates with multiple pathologies. Structural variants affecting RMND5A are candidate genetic determinants in neural tube defects 5. In laryngeal squamous cell carcinoma, IGF2BP3-mediated m6A-dependent RMND5A upregulation promotes tumorigenicity and immune evasion by increasing PD-L1 expression 6. MiR-138 targeting RMND5A regulates miRNA processing by destabilizing Exportin-5 and suppresses cancer cell migration 7.