SFTPD encodes surfactant protein D (SP-D), a collectin pattern recognition molecule essential for innate pulmonary immunity. SP-D binds bacterial lipopolysaccharides, oligosaccharides, and fatty acids, modulating immune responses and facilitating pathogen clearance 1. The protein enhances phagocytosis and regulates leukocyte function while potentially participating in surfactant turnover and extracellular remodeling 2. Serum SP-D levels are strongly genetically influenced, with multiple SFTPD single nucleotide polymorphisms affecting protein expression 2. In preterm infants, the rs1923537 polymorphism associates with reduced respiratory distress syndrome risk and improved oxygen supplementation outcomes 3. SFTPD variants influence disease susceptibility: specific alleles correlate with decreased lung cancer risk in smokers and nonsmokers 4, while serum SP-D levels increase in interstitial lung disease patients 5. Recent studies identified SFTPD as a hub gene facilitating colorectal cancer lung metastasis 6 and incorporated it into a prognostic signature for lung adenocarcinoma 7. However, serum SP-D and common SFTPD variants show limited association with mild-to-moderate asthma in adolescents 8, suggesting context-dependent disease relevance. These findings indicate SFTPD's multifaceted role in respiratory homeostasis, infection defense, and potentially cancer progression.