Cybrd1, also known as duodenal cytochrome b (Dcytb), is a ferric reductase enzyme. It was initially thought to play a crucial role in reducing dietary iron for uptake by the divalent metal ion transport system in the intestine, contributing to dietary iron absorption [4,5,6]. It may also be involved in copper uptake [6].

However, inactivation of the murine Cybrd1 gene in knockout mouse models showed that loss of Cybrd1 had little or no impact on body iron stores, even in iron-deficient conditions, suggesting that other mechanisms exist for dietary iron reduction [4].

In cancer research, in colorectal cancer, DDX17 promotes metastasis and epithelial-mesenchymal transition (EMT) via down-regulation of miR-149-3p, leading to increased CYBRD1 expression [1]. In ovarian cancer, upregulated CYBRD1 expression is associated with poor prognosis, and may be related to increased iron uptake, immune microenvironment regulation, ferroptosis, and ERK signaling pathway [2]. In glioma, increased CYBRD1 expression is associated with aggravated clinical outcomes, and CYBRD1 overexpression enhances glioma cell aggressiveness and attenuates the response to IFN-α [3].

In conclusion, Cybrd1's role in iron absorption may not be as essential as initially thought based on gene knockout mouse models. In diseases like cancer, Cybrd1 is involved in processes such as metastasis, EMT, and immune response modulation, highlighting its significance in understanding cancer development and potentially guiding treatment strategies.