The S100 family of proteins plays a pivotal role in the pathogenesis of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pulmonary arterial hypertension (PAH), pulmonary fibrosis, lung cancers, acute lung injury, acute respiratory distress syndrome, COVID-19, and lung transplantation. The gene discussed is S100B; the disease is COVID-19.