Ifnl3, also known as IL28B, is a gene that encodes a protein belonging to the interferon lambda family. Interferons play crucial roles in the innate immune response, regulating the body's defense against viral infections and modulating immune cell functions. The pathways associated with Ifnl3 are related to antiviral responses and immune regulation, which are of great biological importance in maintaining the body's health [2,4,5,6]. Genetic models can be valuable in studying Ifnl3 to understand its precise functions and implications in disease.

In relation to diseases, Ifnl3 polymorphisms have been extensively studied. In COVID-19 patients, carriers of at least one variant allele of Ifnl3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection, indicating that this polymorphism significantly affects the outcome of COVID-19 [1]. For chronic hepatitis B (CHB) patients, two polymorphisms (rs12979860 and rs8099917) of Ifnl3 may play a crucial role in interferon-based treatment, especially in the HBeAg-positive group [2]. In systemic sclerosis, the Ifnl3 polymorphism is associated with pulmonary fibrosis, and serum IFN-λ3 levels are higher among subjects with pulmonary fibrosis [3]. Regarding hepatitis C virus (HCV) infections, Ifnl3 SNPs are the strongest baseline predictors of sustained virologic response to pegylated interferon and ribavirin therapy in HCV genotype 1, 2, or 3 infections [4,7]. An Ifnl3-adjuvanted HCV DNA vaccine can reduce regulatory T cell frequency and increase virus-specific T cell responses, showing potential in preventing HCV re-infection [8].

In conclusion, Ifnl3 is a key gene in the innate immune response, playing a significant role in various viral-related diseases such as COVID-19, hepatitis B, and hepatitis C, as well as in fibrotic conditions like pulmonary fibrosis in systemic sclerosis. Studies on Ifnl3, especially those involving its polymorphisms, help in understanding disease mechanisms and can potentially guide therapeutic decision-making for these diseases.