Per2, short for Period2, is a core component of the circadian rhythm, playing a crucial role in regulating the circadian rhythm of the biological clock [3]. It is involved in various pathways and physiological systems such as metabolism, sleep, and immune response [4]. Genetic models like the PER2::luciferase (PER2::LUC) knockin mouse have enabled the study of its spatiotemporal patterns in the suprachiasmatic nuclei (SCN) [6].

In oral squamous cell carcinoma (OSCC), PER2 inhibits PD-L1 expression by suppressing the IKK/NF-κB pathway, enhancing the immune response against the cancer [1]. In pituitary tumorigenesis, jetlagged mice with PER2 upregulation have accelerated GH3 xenograft tumor growth, while loss of Per2 protects mice from developing estrogen-induced pituitary adenoma. PER2 promotes pituitary tumorigenesis by inducing the expression of cell cycle genes through enhancing HIF-1α transcriptional activity [2]. In ameloblast differentiation, circadian disruption mice with reduced PER2 expression showed decreased amelogenin expression and enamel matrix secretion. Per2 knockdown in ameloblast-lineage cells also affected cell junctions, enamel matrix secretion, and mineralization [5]. In chondrocytes treated with lipopolysaccharide (LPS), Per2 overexpression increased cell proliferation, inhibited apoptosis and inflammation through the PTEN/PI3K/Akt signalling pathway [7]. In ulcerative colitis, PER2 was decreased in the inflamed mucosa and peripheral blood CD4+ T cells of patients. Overexpression of PER2 in UC CD4+ T cells inhibited IFN-γ production by down-regulating ADAM12 expression [8].

In conclusion, Per2 is essential for regulating the circadian rhythm and is involved in multiple biological processes and disease conditions. Gene knockout and other genetic models in mice have been crucial in revealing its role in diseases such as cancer, oral development-related disorders, and inflammatory bowel diseases, providing potential therapeutic targets for these conditions.