The protein component of surfactant helps in the modulation of the innate immune response, and inflammatory processes.

[11][12][13][14] The lung is the main site of SFTPA2 synthesis, but SFTPA2 mRNA expression has also been detected in the trachea, prostate, pancreas, thymus, colon, eye, salivary gland and other tissues.

[16][17] The expression of SFTPA2 is regulated by cellular factors including proteins, small RNAs (microRNAs), glucocorticoids, etc.

[18] Differences in the SFTPA2 gene sequence at the coding region determine SP-A genetic variants or haplotypes among individuals.

[23] Alterations of the relative levels of SP-A1 and SP-A2 have been found in BALF from patients with cystic fibrosis,[24] asthma,[25] and infection.

[11] SFTPA2 mutations also associated with pulmonary fibrosis via mechanisms that involve protein instability and endoplasmic reticulum stress.

[6] One of the important features of human surfactant protein A mRNAs is that they have a variable five prime untranslated region (5’UTR) generated from splicing variation of exons A, B, C, and D.[29][30] At least 10 forms of human SFTPA2 and SFTPA1 5’UTRs have been identified that differ in nucleotide sequence, length, and relative amount.

This 30-nucleotide long sequence has been shown to enhance both gene transcription and protein translation (biology), and plays a key role in the differential regulation of SFTPA2 and SFTPA1 expression.

[34] The impact of this regulation on SFTPA2 relative protein levels may contribute to individual differences in susceptibility to lung disease.

Exposure of lung cells to particulate matter affects splicing of 5’UTR exons of SFTPA2 transcripts.