A deficiency of BCKDH causes the accumulation of BCAAs and their toxic by-product BCFAs (L-α-hydroxyisovaleric acid, α-ketoisovaleric acid, and 3-methyl-2-oxovaleric acid) in the blood and urine, resulting in a condition known as maple syrup urine disease (MSUD), which accumulates damage in mitochondrial DNA and nuclear DNA and subsequently impairs mitochondrial biogenesis (Aevarsson et al., 2000; Strand et al., 2014). Here, PPM1K is linked to maple syrup urine disease.