Bphl, also known as biphenyl hydrolase-like protein, is a serine hydrolase. It catalyzes the hydrolytic activation of amino acid ester prodrugs of nucleoside analogs such as valacyclovir and valganciclovir [2,3]. It also has the function of detoxifying homocysteine thiolactone, with a much higher catalytic efficiency compared to other related enzymes [5]. Gene knockout mouse models are valuable tools to study its in-vivo functions.

In a study using Bphl knockdown in lung adenocarcinoma cell lines and a nude mouse tumor implantation model, it was found that Bphl knockdown led to decreased cell proliferation, colony formation, and metastasis, increased apoptosis, and altered cell cycle distribution. In nude mice, Bphl knockdown A549 cells showed slower tumor growth, suggesting that Bphl may promote tumor growth in lung cancer [1]. In Bphl knockout mice, valacyclovir was still rapidly and efficiently hydrolyzed to acyclovir, indicating that Bphl is not obligatory for this conversion either presystemically or systemically [4].

In conclusion, Bphl has important functions in the activation of nucleoside analog prodrugs and homocysteine thiolactone detoxification. The use of Bphl knockout mouse models has revealed its potential role in promoting tumor growth in lung cancer and its non-essential role in valacyclovir to acyclovir conversion, providing valuable insights into related biological processes and disease mechanisms.