Evidence is accumulating that implicates folate metabolism in optic neuropathies, particularly those affecting the retinal ganglion cell, making MTHFR a strong autosomal candidate genetic modifier in LHON, despite not localizing to the X chromosome and therefore less likely to contribute directly to the gender bias in LHON. The gene discussed is MTHFR; the disease is Leber hereditary optic neuropathy.