NEIL2, also known as Nei-like 2, is a crucial bifunctional DNA glycosylase. It plays a central role in the base excision repair (BER) pathway, which is essential for maintaining genome integrity by eliminating oxidized DNA base lesions. These lesions can be highly mutagenic, and thus NEIL2 is vital for overall cellular survival and normal biological functions [1,3].

In Neil2-null mice, there is an age-dependent accumulation of oxidative DNA damage, predominantly in the transcribed regions of the genome [5]. These mice are also more sensitive to inflammatory agents, indicating that NEIL2 is important for protecting against inflammation-related pathologies [5]. In SARS-CoV-2 infection, lower levels of NEIL2 are observed in severely infected patients, and recombinant NEIL2 delivery can decrease viral replication and pro-inflammatory gene expression, suggesting its protective role during viral infection [2,4]. Additionally, Neil2-null mice infected with a mouse-adapted CoV-2 strain have more severe viral infection, increased pro-inflammatory gene expression, and higher mortality rates [4].

In conclusion, NEIL2 is essential for maintaining genomic integrity, especially in the transcribed sequences of the genome, and for modulating the immune response. Studies using Neil2-null mouse models have revealed its significance in inflammation-associated pathologies and in the host response to viral infections such as SARS-CoV-2.