To a lesser extent hephaestin has been detected in colon, spleen, kidney, breast, placenta and bone trabecular cells but its role in these tissues remains to be established.

Hephaestin presents homology with ceruloplasmin, a serum dehydrogenase protein involved in copper detoxification and storage.

sla mice harbor a partial deletion mutation of the HEPH gene, resulting in the expression of a hephaestin protein that is truncated by 194 amino acids.

Studies suggest that this truncated hephaestin protein still retains a minimal, yet detectable and quantifiable level of ferroxidase activity.

[12] They demonstrated that recombinant human hephaestin (rhHp) bound copper (determined by inductively coupled plasma mass spectrometry) and exhibited an absorption maximum at ~610 nm consistent with other blue multicopper oxidases such as ceruloplasmin.

By using ferrous ammonium sulfate as a substrate, rhHp was shown to have ferroxidase activity with a Km of 2.1 μM for Fe(II).

[15] The regulation of hephaestin expression and the protein's role in the larger picture of iron metabolism and homeostasis remain an active area of research.

The shared phenotype between the two strains suggests that intestinal hephaestin plays an important role in maintaining whole-body iron homeostasis.