Period circadian protein homolog 2 (PER2)

Period circadian protein homolog 2 (PER2) is a key component of the mammalian circadian clock, highly conserved and expressed in a rhythmic pattern primarily in the suprachiasmatic nucleus and peripheral tissues[3][4]. PER2 forms homo- and heterodimers with other core clock proteins such as PER1, PER3, CRY1, and CRY2, creating a transcriptional/translational feedback loop that regulates the periodicity of biological rhythms[1][3]. It represses the activity of the CLOCK/BMAL1 complex, thereby inhibiting its own expression and that of other target genes. PER2 also has non-circadian roles, including critical functions in cell cycle inhibition, modulation of apoptosis via the p53 pathway, developmental regulation (e.g., mammary gland morphogenesis), and metabolic adaptation[2][4]. It is implicated as a tumor suppressor, as reduced expression is seen in many cancers, and it influences susceptibility to sleep disorders and cardiovascular and metabolic diseases. PER2 stability and function are modulated by phosphorylation via casein kinase 1 epsilon, and its expression can be regulated by glucocorticoids, linking circadian rhythm with stress responses and endocrine signaling[1][3]. No approved drugs directly target PER2, but its pathway is sensitive to agents targeting the circadian machinery or upstream signaling (such as CK1ε inhibitors or glucocorticoids). Considerable therapeutic and safety challenges exist due to its central role in physiological homeostasis.

Other names

Period protein homolog 2PER2Period circadian protein 2Circadian rhythm protein period 2

Drugs indirectly affecting PER2 may act via modulation of the circadian clock, especially glucocorticoids which regulate PER2 expression through glucocorticoid response elements[3]. - Casein kinase 1 epsilon (CK1ε) phosphorylates PER2, affecting its stability and consequently modulating circadian rhythm; thus, CK1ε inhibitors may influence PER2 function[3].