[10] This discovery provided a tool for other scientists to perform research on biological clocks and was an important early development in the field.

[17] The glycine rich P-loop is between the β1 and β2 strands, forming a classical β-strand-turn-β-strand motif that anchors and clamps the alpha phosphate of ATP.

[15] This autophosphorylation occurs in the protein's C-Terminal domain, a region believed to behave as a pseudosubstrate, and inhibits kinase activity.

[23] Daily oscillations in protein and mRNA transcription have been observed in many cells, including the mammalian master clock known as the suprachiasmatic nucleus (SCN).

[24] However, unlike most circadian rhythm proteins that oscillate in their expression, casein kinase 1 epsilon is constitutively active.

[23] The core proteins that comprise the mammalian TTFL include Period (PER), Cryptochrome (CRY), BMAL1, CLOCK, and casein kinase 1 epsilon.

[26] Phosphorylation also hinders PER's ability to enter the nucleus by inducing a conformational change in its nuclear localization sequence.

[23] Casein kinase 1 results in a cyclic expression of mammalian oscillator proteins, resulting in a timekeeper (mammalian oscillator) for the cell:[32] The prominent phenotype in the CK1ε tau mutant hamsters discovered by Menaker was an unusually short free-running period — 22 hours in heterozygotes, and 20 hours in homozygotes for the mutation—making this allele semidominant.

[10] In humans, mutations affecting the PER2 phosphorylation site of the CK1ε and/or CK1δ gene result in Familial Advanced Sleep Phase Syndrome (FASPS).

[38][39] This mutation, S662G, which results in the loss of a single phosphate acceptor site on PER2, prevents CK1ε protein from binding to PER and leads to an unusually short circadian period.

[42] Two circadian rhythm functional homologs of this mammalian protein can be found in Drosophila melanogaster (fruit fly).

One gene, coding for the protein Doubletime (abbreviated dbt), serves a similar purpose to casein kinase 1 epsilon in chronobiology, as it plays a role in the phosphorylation of PER.

[7][15][43][44] In addition, casein kinase 1 epsilon does not completely rescue circadian rhythms in fruit fly doubletime knockouts (dbt -/-), suggesting that these enzymes serve similar, but not identical, functions.

[46] Conversely, Gsk3 is also found in mammals, and mutants have been implicated in circadian rhythm abnormalities in patients suffering with bipolar disorder.

[7] The Drosophila melanogaster genome contains other casein kinase 1 family enzymes, which are believed to serve no circadian function.

[42] In this manner, temporally sequenced phosphorylations of PER2 act to delay its degradation rate and may provide insight into how the circadian clock is temperature compensated.

[42] Mutations to this site can affect the ability of PER2 to receive a priming phosphorylation, leading to a lengthening or shortening of period.

[42] Mutations in the phosphorylation area of PER2 are thought to be related to FASPS patients[50] The canonical Wnt Pathway involves the accumulation of β-catenin in the cytoplasm, which activates transcription factors.

[7][53] Casein kinase 1 epsilon and delta are known to phosphorylate a tumor suppressor protein, p53 in vivo in both humans and murine, or old world rats.

[59] Several studies have demonstrated a connection between molecular components of the circadian clock and psychiatric disorders, particularly drug abuse.

PF-670462, developed by Pfizer, is a well-characterized inhibitor of both CK1ε and CK1δ that has been shown to lengthen the period of circadian rhythms when administered in vitro to rat fibroblasts and COS cells, and to mice in vivo.

However, its ability to lengthen circadian rhythms is weaker than that of PF-670462 in both the in vitro rat fibroblasts and in vivo mice models.