CDKL

Despite their names, CDKL kinases do not require cyclins for activity. The five human members, CDKL1 through CDKL5, carry an N-terminal extension ahead of the catalytic domain and branch separately from classical CDKs within the CMGC group. CDKL5 is best characterized: it is nuclear in neurons, phosphorylates microtubule-associated and synaptic proteins, and loss-of-function mutations cause CDKL5 deficiency disorder, an X-linked developmental and epileptic encephalopathy with seizures in the first months of life. CDKL1 and CDKL2 are broadly expressed but their physiological substrates are unresolved, and CDKL3 has reported nuclear functions. Because these enzymes remain orphan-like, recombinant CDKL proteins are used mainly for substrate discovery and antibody specificity testing.