Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.

Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type III and IV intermediate filaments, the phosphorylation of the N-terminal head domain by the secondary messenger-dependent kinase proteins influences the phosphorylation of the C-terminal tail, that aids in their disassembly.

During mitosis, the transition from prophase to pro-phase results in the nuclear lamins, vimentin, and glial fibrillary acidic proteins undergoing site-specific phosphorylation by Rho kinase, Cdk1, Aurora-B, and PAK1, resulting in disassembly. The phosphorylation of lamins A, B, and C leads to depolymerization of the filaments into lamin dimers, further leading to nuclear membrane disintegration. The lamins remain attached to the disintegrated membrane through their C-terminal prenylation. The removal of phosphates through phosphatase leads to the reassembly of the lamin meshwork during the telophase.