MXRA8 (matrix remodeling associated 8) functions primarily as a cell surface receptor for multiple arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro, and O'nyong nyong viruses 1. The protein contains two immunoglobulin-like domains arranged in a unique disulfide-linked head-to-head configuration 2. MXRA8 mediates viral entry by binding directly to viral particles and enhancing virus attachment and internalization into cells 1. Structurally, MXRA8 binds by wedging into a cleft between two adjacent viral E2-E1 heterodimers on the virus surface, with both domains and the hinge region participating in the interaction 3. The receptor shows vertebrate class-specific binding modes, with mammalian and avian MXRA8 variants displaying distinct engagement patterns with different alphavirus groups 4. MXRA8 plays a critical role in alphavirus pathogenesis, as genetic ablation in mice reduces viral infection of musculoskeletal tissues and associated inflammatory responses 5. Beyond viral infection, MXRA8 has been identified as a novel bone metabolism-related gene in human femoral head tissue 6 and shows causal association with inflammatory bowel disease risk 7. The receptor represents a promising therapeutic target, as MXRA8-blocking antibodies and fusion proteins can inhibit viral infection both in vitro and in vivo 1.