LDLRAD3 (low density lipoprotein receptor class A domain containing 3) is a highly conserved membrane receptor that serves as a critical entry factor for alphaviruses, particularly Venezuelan equine encephalitis virus (VEEV) 1. The protein functions as a viral receptor by directly binding to VEEV particles and enhancing virus attachment and internalization into host cells through receptor-mediated endocytosis 1. Structural studies reveal that domain 1 of LDLRAD3 (LDLRAD3-D1) has a cork-like structure that inserts into clefts between adjacent viral E2-E1 heterodimers through hydrophobic and polar contacts 2. This domain is both necessary and sufficient to support VEEV infection 1. LDLRAD3 is essential for VEEV pathogenesis, as mice with Ldlrad3 deletions show markedly reduced viral infection of neuronal cells and survive intranasal and intracranial VEEV inoculation 13. Beyond viral infection, LDLRAD3 appears to play roles in vascular dementia, where it is upregulated in endothelial cells and associated with MAPK signaling pathways and lipid metabolism 4. The receptor has also been identified as a potential alternative entry factor for SARS-CoV-2 in ACE2-independent pathways 5.