Clock proteins govern circadian physiology and their function is regulated by a variety of signaling pathways. Here, we show that p45^PFK^, a previously reported circadian rhythmic kinase, corresponds to CK2[alpha]. Rhythmic phosphorylation of the core clock protein BMAL1 by CK2[alpha] occurs in the suprachiasmatic nuclei (SCN), the mammalian central pacemaker. Circadian BMAL1 phosphorylation controls its nucleocytoplasmic localization. Gene silencing for CK2[alpha] and BMAL1 mutagenesis of a highly conserved CK2 phosphorylation site (Ser 90) result in impaired BMAL1 accumulation in the nucleus and subsequent disruption of clock function. These findings reveal that circadian rhythmic kinase CK2 is an essential regulator of the mammalian circadian system
