Egln1, also known as PHD2 (prolyl hydroxylase domain-containing protein 2), is a prolyl hydroxylase enzyme. It functions as an oxygen sensor and plays a central role in the hypoxia-inducible factor (HIF)-mediated hypoxia signaling pathway. Under normoxia, Egln1 catalyzes prolyl hydroxylation of HIF-1α, leading to its proteasomal degradation [2].

In breast cancer, Egln1 accumulates on mitochondria under hypoxia. Its β2β3 loop region is responsible for mitochondrial translocation and contributes to tumor growth. Egln1 interacts with AMP-activated protein kinase alpha (AMPKα) on mitochondria, and this interaction is essential for their mutual mitochondrial translocation. Under normoxia, Egln1 prolyl-hydroxylates AMPKα, and they dissociate, while hypoxia leads to their constant interaction and accumulation, activating AMPKα phosphorylation and ensuring metabolic homeostasis and breast tumor growth [1].

In osteocytes, conditional loss of Phd2 (Egln1) in vivo upregulated Fgf23, suggesting Egln1 is a critical mediator of osteocyte FGF23 production, which may provide new therapeutic targets for skeletal diseases involving disturbed oxygen/iron sensing [3].

In nasopharyngeal carcinoma, Egln1 promotes tumorigenesis and radioresistance by facilitating degradation of tumor protein p53 through the ubiquitination system in a hydroxylase-dependent manner [4].

In conclusion, Egln1 is crucial in oxygen sensing and multiple biological processes. Its functions are revealed through in vivo studies such as gene knockout models in various disease areas including breast cancer, skeletal diseases, and nasopharyngeal carcinoma. These models help us understand its role in tumor growth, metabolism, and biomineralization, providing potential therapeutic targets for related diseases.