Neuronal Cdc2-like kinase, Nclk, is a heterodimer of cyclin-dependent protein kinase 5 (Cdk5) and a 25-kDa essential regulatory subunit that is derived from a 35-kDa brain- and neuron-specific protein. This protein is called neuronal Cdk5 activator, p25/35nck5a. Nclk is one of the best characterized Cdc2 family kinases whose primary function is not cell cycle related. It has been suggested that this protein kinase plays important roles in neurocytoskeleton dynamics and its loss of regulation has been implicated in Alzheimer pathology. As a member of the Cdc2-like kinase family, Nclk shares many common properties with other members of the Cdc2-like kinase family. It also possesses unique characteristics that may be related to its distinct and noncell cycle related functions. The regulatory and functional properties of Nclk are reviewed in this communication.