SFTPA2 encodes surfactant protein A2, a calcium-binding protein essential for lung function. In the presence of calcium ions, SP-A2 binds surfactant phospholipids and reduces surface tension at the air-liquid interface in alveoli, enabling normal respiration. SP-A2 also plays a critical role in innate immunity and host defense against respiratory pathogens 1. Functionally, SP-A1 and SP-A2 exhibit divergent roles; both gene products are required together to form tubular myelin structures in vivo, which are important for surfactant organization 2. SFTPA2 expression is differentially regulated through 3' untranslated region polymorphisms that modulate microRNA binding, affecting gene expression levels across individuals 3. Pathogenic SFTPA2 mutations cause interstitial lung disease through defective protein secretion, with highly variable disease severity ranging from asymptomatic carriers to cases requiring lung transplantation at median age 51 years 4. Notably, SFTPA2 variant carriers face markedly elevated lung cancer risk (odds ratio 3.97 compared to non-carriers, and 18.1-fold higher risk versus telomere-related gene variant carriers), predominantly presenting as adenocarcinoma, with median overall survival of 24 months 5. Additionally, plasma SFTPA2 levels associate with lung cancer incidence, detectable more than seven years before diagnosis in prospective analyses 6. SFTPA2 variants also influence susceptibility to tuberculosis, with specific polymorphisms showing significant protective or risk associations 1.