The microtubule (MT) cytoskeleton functions in cytoplasmic organization, cellular movement, determination of cell polarity, intracellular transport, and chromosome segregation. Dynamic instability, continuous cycles of MT assembly (stabilization) and disassembly, mediates MT participation in these events. The function of MTs, particularly stabilization, is regulated by MT-associated proteins (MAPs). A subfamily of MAPs, called AP-MAPs (assembly promoting MAPs), includes tau, MAP2, and MAP4. These proteins are classified as type II MAPs and contain a C-terminal MT binding domain with 3 to 5 imperfect repeats of an 18 amino acid motif. While tau and MAP2 are specifically expressed in neuronal cells, MAP4 is the major MAP of nonneuronal mammalian cells. MAP activity and interaction with MTs are regulated by MARK (MAP/MT affinity-regulating kinase) and mapmodulin. MARK-mediated phosphorylation of MAPs on their homologous KXGS motifs results in detachment of MAPs from MTs and MT disruption. In addition, mapmodulin tightly interacts with the MT-binding domains of MAPs and hinders MAP binding to MTs. Thus, MAP4 is a highly regulated type II MAP that controls MT assembly and disassembly.