CK1δ and CK1ε have been shown to be relevant in human disease. Recent findings indicate that pharmaceutical inhibition of CK1 may be a promising therapeutic for aberrant circadian rhythm. Mutations and variants of the CK1ε phosphorylation site of PER2 are associated with cases of Familial Advanced Sleep Phase Syndrome (FASPS).  Similarly, length variations in the CK1ε phosphorylation site of PER3 have been found to correlate with morningness and eveningness; longer alleles are associated with early risers while shorter alleles are associated with late risers.  Additionally, 75% of patients with Delayed sleep phase syndrome are homozygous for the shorter allele.
Mutations in CK1 have been shown to alter circadian behavior in other mammals, as well.  In 1988, the golden hamster tau mutant, which has a freerunning period of 22hrs,  was the first mammalian circadian mutant discovered. Twelve years later in 2000, the tau mutation was mapped to CK1ε. Since its discovery, the tau mutant has proven to be a valuable research tool in circadian biology. CK1ɛ, a T178C substitution, is a gain-of function mutation that causes an increase in degradation of PER, but not CRY. This creates a disruption in the PER-regulated feedback loop and consequently an acceleration of molecular oscillations. 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). Recent research has also identified a link between mutations in the CK1δ gene and familial migraine and advanced sleep phase, a finding that was replicated in mice migraine models.