MAP6 is a multifunctional microtubule-associated protein with primary roles in neuronal cytoskeletal organization and synaptic function. Its canonical function involves microtubule cold stabilization 1, a property distinct from other MAPs like tau and MAP2. MAP6 stabilizes microtubules through calmodulin-regulated bifunctional binding motifs 1 and regulates dendritic morphogenesis by controlling lysosomal trafficking via interaction with FTLD-TDP risk factor TMEM106B, acting as a molecular brake on retrograde lysosomal transport 2. Beyond microtubule binding, MAP6 functions through microtubule-independent mechanisms. It mediates axonal growth via Semaphorin 3E signaling through proline-rich domains and SH3 protein binding 3, and stabilizes Kv3.1 voltage-gated potassium channels in parvalbumin-positive interneurons, regulating behavior, emotion, and memory 4. MAP6 also localizes to non-microtubular compartments including the Golgi apparatus, plasma membrane, and mitochondria 5. Clinically, MAP6 dysfunction is implicated in schizophrenia, where prefrontal cortex mRNA upregulation and genetic associations have been detected 6, and MAP6-deficient mice display neuroleptic-responsive behavioral defects 1. TMEM106B variants linked to frontotemporal lobar degeneration may exert pathogenic effects through disrupted MAP6-mediated lysosomal trafficking 2.