CDHR3 is a cadherin-family adhesion molecule that functions primarily as a cellular receptor for human rhinovirus C (HRV-C) 1. Located on ciliated respiratory epithelial cells 2, CDHR3 mediates viral entry and replication through direct binding interactions with HRV-C particles 3. A common coding variant (rs6967330) increases CDHR3 surface expression, enhancing HRV-C susceptibility and promoting respiratory infections 1. CDHR3 dysfunction directly impacts disease severity in early childhood respiratory illnesses. Genetic variants in CDHR3 are associated with severe childhood asthma exacerbations, persistent preschool wheeze, and bronchiolitis susceptibility, particularly for non-RSV viral infections 45. Notably, CDHR3 variants interact with GSDMB polymorphisms to amplify asthma risk through enhanced IL-17A responses to viral stimulation 6. CDHR3 knockout in primary airway epithelial cells reduces HRV-C infection by 80% while maintaining normal ciliated cell differentiation 2, confirming its necessity for viral pathogenesis. Therapeutic targeting via anti-CDHR3 antibodies significantly reduces viral growth in respiratory organoids and protects transgenic mice from lethal HRV-C infection 37, establishing CDHR3 as a promising therapeutic target for HRV-C-related respiratory diseases.