[6][7][9] These subunits evolved from a common prokaryotic ancestor via gene duplication and mutation events.

Generally, the N-terminal of the subunits carries out their catalytic activity while the C-terminal contains allosteric ligand binding sites.

[6][9][14] Notably, mutations in PFKM have been shown to cause Tarui disease due to homozygosity for catalytically inactive M subunits.

[7] Even though PFKM functions to drive glycolysis, its overexpression has been associated with type 2 diabetes and insulin resistance in skeletal muscle.

One possible explanation suggests that the overexpression is meant to compensate for the allosteric inhibition of PFK1 as a result of excess oxidation of free fatty acids and accumulation of citrate and acetyl-CoA.