[6] In the human brain, the enzyme is distributed widely, mostly in neuronal cell bodies, as well as in astrocytes and oligodendrocytes.

[6] The C-term-EH hydrolyzes one important class of lipid signaling molecules that includes many epoxyeicosatrienoic acids (EETs) that have vasoactive, anti-inflammatory and analgesic properties.

Studies using a lipid epoxide as a substrate detected this activity in the soluble fraction of multiple organs, though at a lesser amount than in liver and kidney.

[6] Conversely, the sEH plays a major role in the in vivo metabolism of endogenous lipid epoxides, such as the EETs and squalene oxide, a key intermediate in the synthesis of cholesterol.

[15] The DHETs are more readily excreted, but they have yet to be fully characterized, and may possess biological properties themselves, complicating the balance of signals described in the simplified model.

[11][24] The phosphatase activity of sEH has been shown to hydrolyze in vitro lipid phosphates such as terpene pyrophosphates or lysophosphatidic acids.

[6] Studies suggest a potential role of sEH in regulating cholesterol biosynthesis and metabolism in the brain.

Through metabolism of EETs and other lipid mediators, sEH plays a role in several diseases, including hypertension, cardiac hypertrophy, arteriosclerosis, brain and heart ischemia/reperfusion injury, cancer and pain.

[15] Because of its possible role in cardiovascular and other diseases, sEH is being pursued as a pharmacological target, and potent small molecule inhibitors are available.

[27] EicOsis designs and applies sEH inhibitors towards treating chronic pain in humans, companion animals and horses.

The inhibitor EC1728 has been shown to successfully treat equine laminitis and alleviate inflammatory pain in dogs and cats and is currently undergoing clinical trials in horses.

The sEH inhibitor EC5026 has been selected as the therapeutic for diabetic neuropathy and recently entered Phase 1 clinical trials.

Another drug described as a small-molecule thrombolytic with multiple mechanisms of action, SMTP-7, has been found to act as a sEH inhibitor, but is still at early experimental stages.