Upstream transcription factor 1 (USF1) gene is located in the chromosome region (1q21-q25) that is notable for being the most consistently replicated linkage to type 2 diabetes and metabolic syndrome. The gene encoding USF1, a ubiquitously expressed transcription factor of the basic helix-loop-helix leucine zipper family, which is a key regulator of numerous genes involved in lipid and glucose metabolism, is regarded as an attractive candidate gene for several complex diseases with defective glucose and/or lipid metabolism, including type 2 diabetes and the metabolic syndrome. Here, we review the structures, the characters of biological functions of the USF1 gene, as well as its association with metabolic syndrome related traits.