Oxygen-sensitive Proline Hydroxylase (PHD) regulates Hypoxia-inducible factor (HIF-1α), which is known to be an important regulator of cellular oxygen homeostasis. Under hypoxic conditions, PHD is inhibited, leading to the accumulation of HIF-1α, translocation into the nucleus, and binding to HIF-1β to form a heterodimer that acts as a transcription factor thereby inducing mitophagy. HIF-1α was recognized as a protective regulator of Inflammatory Bowel Disease (IBD) by inducing the expression of gut barrier protective genes, and PHD have been identified as promising therapeutic targets in IBD.

The hypoxia-inducible factors (the "HIF") are transcription factors that function as master regulators of oxygen homeostasis. When oxygen availability is limited, or during hypoxia, HIFs are stabilized to drive a transcriptional process by binding to hypoxia-responsive element (the "HRE") that promotes hypoxia adaptation. The final molecular step that controls HIFs stabilization converges on prolyl hydroxylases (the "PHDs").

Inhibition of PHD triggers erythropoiesis by inducing both renal and hepatic Erythropoietin (EPO) synthesis, which stimulates the production of red blood cells in the bone marrow and regulates the metabolism of iron, an indispensable component of functional red blood cells. Inhibition of PHD could also suppress the production of hepatic hepcidin, which has negative effects on iron mobilization. Inhibition of PHD might upregulate the expression of several iron metabolism genes. Thus, inhibition of PHD addresses both impaired EPO production and functional iron deficiency.