CSNK1D

CSNK1D, or casein kinase I delta, is a human gene that encodes the enzyme casein kinase 1 delta (CK1δ). CK1δ is a serine/threonine kinase belonging to the CK1 family and is expressed broadly in many tissues. The protein participates in a wide range of cellular processes through phosphorylation of diverse substrates and exists in multiple isoforms produced by alternative splicing. CK1δ activity is regulated by autophosphorylation and by interactions with regulatory proteins and other signaling pathways.

A central role for CK1δ is in the regulation of circadian rhythms. Along with CK1ε, CK1δ phosphorylates clock proteins such as PER1, PER2, and PER3, leading to their degradation or altered cellular localization and thereby shaping the timing of the circadian clock. Beyond the clock, CK1δ participates in Wnt signaling by phosphorylating Dishevelled and other components, influencing downstream effects on gene expression. The kinase also contributes to DNA damage response, vesicle trafficking, endocytosis, and the phosphorylation of tau, linking it to pathways implicated in neurodegenerative disease.

Genetic and clinical context: CSNK1D variants have been reported in individuals with neurodevelopmental disorders and epilepsy in some studies, though the overall contribution of CSNK1D to disease risk and its penetrance require further study. Functional studies indicate that altering CK1δ activity can impact circadian timing and signaling pathways.

Research and therapeutic context: CK1δ activity can be modulated with small-molecule inhibitors used in research to study circadian regulation; such inhibitors have also been explored as potential therapeutic leads for sleep disorders and cancer. Ongoing research continues to clarify CSNK1D’s roles in development and disease.