A Comprehensive Review of Casein Kinase 2 in Drosophila Circadian Timing and Its Biomedical Relevance

Circadian rhythms are endogenous 24-hour oscillations that regulate physiology, metabolism, sleep-wake cycles, and cellular homeostasis. Drosophila melanogaster, a genetically tractable model organism, has played a foundational role in uncovering the molecular mechanisms of circadian rhythms. The discovery of major clock genes, including period (per), timeless (tim), clock (clk), cycle (cyc), double time (dbt), and regulators such as Casein kinase 2 (CK2), emerged primarily from Drosophila research. CK2 operates as a critical post-translational regulator of PER protein phosphorylation, stability, nuclear entry, and degradation. Because PER dynamics dictate the timing and robustness of circadian rhythms in both flies and mammals, altered CK2 activity can profoundly impact rhythmic behaviour. CK2 dysregulation contributes not only to circadian disruption in Drosophila but also models broader pathological processes relevant to cancer, metabolic disease, neurodegeneration, and psychiatric disorders. This review synthesises CK2's molecular role in the Drosophila clock system, includes insights from computational modelling of CK2-PER dynamics, integrates tables throughout the text, and summarises the implications of dysregulated PER phosphorylation for human health.