Isoforms range from 22 to 55 kDa and have been identified in the membranes, nucleus, and cytoplasm of eukaryotes and additionally in the mitotic spindle in mammalian cells.

In contrast, in several important targets, NF-AT[10] and beta-catenin,[11][12] CKI does not require n − 3 priming but, instead, phosphorylates the first serine in the sequence S-L-S, which is followed by a cluster of acidic residues, albeit less efficiently than the optimal sites.

[13] Casein kinase activity was found to be present in most cell types and to be associated with multiple enzymes.

Casein kinase 1 epsilon has been suggested to play a role in phosphorylation of Disheveled in the Wnt signaling pathway.

They found two DBT mutants that had abnormal free-running periods and one that was pupal-lethal but resulted in accumulations of hypophosphorylated PER protein.

[21] Homologs were subsequently identified in mice,[22] and characterisation shows it plays a similar role to that proposed for Drosophila.

[23][24] In 2021, scientists reported the development of a light-responsive days-lasting modulator of circadian rhythms of tissues via Ck1 inhibition.

[25][26] DBT has been shown to physically interact with PER in vitro and in vivo, and to create a stable complex with PER throughout the circadian cycle.

[27] Enhanced PER degradation in the cytoplasm is predicted to delay nuclear translocation of both PER and TIM, and to thus affect the period of circadian rhythms.

The mutation dbtS, associated with a proline to serine substitution at residue 47 [P47S], shortens period length by about 6 h. dbtL contains an amino acid substitution of isoleucine for methionine at residue 80 (M80I) and lengthens period to 29 h.[27] A third mutation, dbtAR, is associated with a change from histidine 126 to tyrosine and causes arrhythmia.

[29][30][31] In the negative feedback loops, CK1ε periodically binds to and phosphorylates the PER proteins (PER1, PER2, and PER3), which form heterodimers with each other and interact with CRY1 and CRY2.

[28] Phosphorylation of the PER proteins also leaves them unable to enter the nucleus, where they suppress transcription of clock genes.

Recent findings indicate that pharmaceutical inhibition of CK1 may be a promising therapeutic for aberrant circadian rhythm.

[35] Mutations and variants of the CK1ε phosphorylation site of PER2 are associated with cases of Familial Advanced Sleep Phase Syndrome (FASPS).

Homozygous mutants (CK1ε(tau/tau)) show a significant decrease in period, both in vivo (behaviorally) and in vitro (measured by firing rates of the suprachiasmatic nucleus).

[41] Also, CK1α has recently been suggested to play a role redundant to CK1δ in phosphorylating PER1[37] although this is not consistent with other data[44] CKIα or CKIδ is essential in modulating the nuclear export of eukaryotic translation initiation factor 6 (eIF6), a protein with essential nuclear and cytoplasmic roles in biogenesis of the 60S subunit of the eukaryotic ribosome.