Rad54l2, also known as RAD54 like 2, is a significant factor involved in maintaining genome stability. It acts in pathways related to DNA repair, especially in resolving TOP2-DNA adducts. It is associated with the TOP2-specific DNA damage avoidance pathway, which is crucial for preserving genome integrity in response to topoisomerase 2 poisons. It also plays a role in regulating the expression of ACE2, which is the host receptor for SARS-CoV-2 infection [1,2,3].

RAD54L2 deficiency confers unique sensitivity to treatment with TOP2 poisons, indicating its importance in the TOP2-related DNA damage response. Knockout of TRAF3, DYRK1A, or RAD54L2 reduces the mRNA levels of ACE2 and inhibits the cellular entry of SARS-CoV-2, showing its role in the regulation of ACE2 expression [2,3]. Additionally, RAD54L2 polymorphisms, such as rs9864693, are associated with an increased risk of lung cancer in the Chinese Han population [4].

In conclusion, Rad54l2 is essential for genome stability through its role in TOP2-DNA adduct resolution and DNA damage avoidance. It also has implications in viral infection through ACE2 regulation and in cancer susceptibility. Studies using gene knockout models, such as the RAD54L2 deficiency models, have been crucial in revealing its functions in these biological processes and disease conditions, providing insights for potential therapeutic strategies in cancer and viral infection [1,2,3,4].