TMEM198 is a transmembrane scaffold protein with dual roles in cellular signaling and viral pathogenesis. In canonical Wnt signaling, TMEM198 promotes LRP6 phosphorylation by recruiting casein kinase family proteins to the plasma membrane, facilitating Wnt pathway activation essential for embryonic development and tissue patterning 1. The protein's cytoplasmic domain mediates association with LRP6, enabling LRP6 phosphorylation at critical residues 1. During embryogenesis, TMEM198 is required for Wnt-dependent neural crest formation and anterior-posterior axis patterning in Xenopus 1. Beyond developmental signaling, TMEM198 has emerged as a critical host factor for coronavirus replication. A genome-wide CRISPR screen identified TMEM198 as essential for double-membrane vesicle (DMV) formation during swine alphacoronavirus and murine betacoronavirus infection 2. TMEM198 directly binds nonstructural proteins nsp3c and nsp4, with its N-terminal 35 amino acids being critical for DMV biogenesis and viral replication 2. TMEM198 deletion reduces viral infection susceptibility in cultured cells and in vivo 2. Additionally, TMEM198 has been identified as a candidate gene associated with plague resistance in natural prairie dog populations, suggesting pathogen-driven selection on this host factor 3.