Casein kinase 1 (CK1) (CK1)

Casein kinase 1 (CK1) is a highly conserved family of serine/threonine-selective protein kinases, including isoforms alpha, delta, epsilon, and gamma, that function as monomeric enzymes independent of second messengers [1, 2, 12]. They play critical roles in diverse cellular processes such as Wnt and Hedgehog signaling, circadian rhythm regulation, DNA repair, and cell cycle progression by phosphorylating a wide array of substrates [1, 5, 8, 12]. Dysregulation of CK1 isoforms is linked to various pathologies, most notably hematological malignancies like myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as solid tumors and neurodegenerative diseases like Alzheimer's [1, 6, 8, 16]. In drug development, CK1 alpha is a key target of the molecular glue degrader lenalidomide in MDS with del(5q), while other isoforms like CK1 delta and epsilon are targeted by small molecule inhibitors for cancer and sleep disorders [2, 8, 16, 20]. Therapeutic challenges include achieving isoform selectivity to avoid systemic toxicity, particularly regarding hematopoietic stem cell maintenance and circadian stability [2, 8, 16].

Other names

Casein kinase ICSNK1 familyCKI

Inhibition of kinase activity through ATP-competitive binding or induction of proteasomal degradation via molecular glue mechanisms [8, 12, 16].