In 2001, Michael Brownlee presented an elegant unifying theory recognizing four key biochemical pathways that mediate hyperglycemia-induced micro- and macrovascular complications in T2DM: increased polyol pathway flux, the increased formation of Advanced Glycation End products (AGEs), increased hexosamine pathway activation and the activation of Protein Kinase C (PKC) isoforms. The gene discussed is PRRT2; the disease is Hyperglycemia.