PER2 is a protein in mammals encoded by the PER2 gene. PER2 is noted for its major role in circadian rhythms. Discovery The per gene was first discovered using forward genetics in Drosophilla melanogaster in 1971. Mammalian Per2 was discovered by in 1997 through a search for homologous cDNA sequences to PER1. It is more similar to Drosophila per than its paralogs. Later experiments in also identified Per2 in humans. Function PER2 is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian clock, which regulates the daily rhythms of locomotor activity, metabolism, and behavior. Circadian expression of these genes and their encoded proteins in the suprachiasmatic nucleus. Human PER2 is involved in human sleep disorder and cancer formation. Lowered PER2 expression is common in many tumors cells within the body, suggesting PER2 is integral for proper function and decreased levels promotes tumor progression. PER2 contains glucocorticoid response elements (GREs) and a GRE within the core clock gene PER2 is continuously occupied during rhythmic expression and essential for glucocorticoid regulation of PER2 in vivo. Mice with a genomic deletion spanning this GRE expressed elevated leptin levels and were protected from glucose intolerance and insulin resistance on glucocorticoid treatment but not from muscle wasting. PER2 is an integral component of a particular glucocorticoid regulatory pathway and that glucocorticoid regulation of the peripheral clock is selectively required for some actions of glucocorticoids. PER2 expression in mice is increased by exposure to 13000 lumens of intense daylight such as Sunshine while decreasing Troponin levels in equal opposite amounts. PER2 in turn enhances oxygen-efficient glycolysis and hence provides cardioprotection from ischemia. Therefore, it is speculated that strong light may reduce the risk of heart attacks and decrease the damage after experiencing one. Moreover, PER2 has protective functions in liver diseases, as it antagonizes hepatitis C viral replication. Per2 knockout mice experience a free-running period of around 21.8 hours, compared to the normal mouse free-running period of 23.3 hours. Some of the Per2 knockout mice can also become arrhythmic under constant light conditions. PER2 has also been shown to be possibly important in the development of cancer. PER2 expression is significantly lower in human patients with lymphoma and acute myeloid leukemia. The PER2 protein seems to be important for