Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1. Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity. Required for bundling actin filaments around the nucleus. Homodimer. Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends. Isoform 2 interacts (via N-terminus) with ACTN2. Isoform 2 interacts (via N-terminus) with PLEC (via N-terminus). Isoform 5 interacts (via N-terminus) with COL17A1 (via cytoplasmic region). Isoform 5 interacts (via N-terminus) with ITGB4 isoform beta-4a (via cytoplasmic region). Isoform 5 interacts (via N-terminus) with ERBIN (via C-terminus). Isoform 5 associates (via C-terminal) with KRT5-KRT14 (via rod region) intermediate filaments of keratins (By similarity). Isoform 2 and isoform 6 can homodimerize (via N-terminus). Isoform 2 interacts (via N-terminus) with PLEC (via N-terminus). Interacts with the neuronal intermediate filament protein, PRPH. Interacts with DES. Interacts with SYNE3. Isoform 1 interacts with TMEM108 (PubMed:17287360). Associates with axonal microtubules at the growing distal tip and intermediate filaments, but not with actin cytoskeleton, in sensory neurons (By similarity). Associates with intermediate filaments, actin and microtubule cytoskeletons. Localizes to actin stress fibers and to actin-rich ruffling at the cortex of cells. Colocalizes both cortical and cytoplasmic actin filaments (PubMed:19932097). Localizes to vesicule-like structures associated with microtubules (PubMed:14581450, PubMed:17287360). Localizes to microtubules and actin microfilaments throughout the cytoplasm and at focal contact attachments at the plasma membrane. Colocalizes with the epidermal KRT5-KRT14 intermediate filaments network of keratins. Colocalizes with ITGB4 at the leading edge of migrating keratinocytes (By similarity). Localizes to actin and intermediate filaments cytoskeletons. Associates with actin cytoskeleton in sensory neurons (By similarity). Localizes to actin and intermediate filaments cytoskeletons. Localizes to central actin stress fibers around the nucleus and is excluded form focal contact sites in myoblast cells. Translocates to the nucleus. Isoform 1 and 2 are expressed in striated and heart muscle cells. Isoform 5 is expressed in the skin. Isoform 6 is expressed in sensory neural cells of the dorsal root ganglion and with low level in the skin (at protein level). Isoform 1 is expressed predominantly in the brain and spinal cord with low levels in the heart (PubMed:14581450). Isoform 2 is predominantly expressed in muscle and heart and with low levels in the brain. Isoform 5 is expressed in the skin and with low levels in myoblast cells. Isoform 6 is expressed in neurons. Isoform 7 is expressed in lung and with low levels in the brain. Isoform 1 is the major form expressed in the dorsal root ganglia at 14.5 dpc. Isoform 2 is predominantly expressed in the myocardium, skeletal muscles, bone cartilage and epithelia of the tongue at 14.5 dpc. Isoform 5 is expressed at high levels in the epidermis and mucosal epithelia of the digestive tracts at 14.5 dpc. Its association with epidermal and simple keratins is dependent on the tertiary structure induced by heterodimerization of these intermediate filaments proteins and most likely involves recognition sites located in the rod domain of these keratins. The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends. Mice show progressive deterioration in motor function and sensory neurodegeneration. Exhibit axonal swellings packed with disorganized intermediate filaments (IFs) and microtubules. Show poorly defined Z lines and display a reduction in sarcomere length. Have increased accumulation of vesicles and severely disrupted retrograde axonal transport. In stratified epithelia, hemidesmosomes are normal but they lack the inner plate and have no cytoskeleton attached. Incomplete sequence. Transmembrane protein (helical transmembrane domain from amino acid 18 to 38). Incomplete sequence. Probably myristoylated on Gly-2. Probably S-palmitoylated on Cys-5 and Cys-7. Mutagenesis of Gly-2 to Ala inhibits cortical localization. Mutagenesis of Cys-5 to Ser inhibits cortical localization. Mutagenesis of Cys-7 to Ser inhibits cortical localization. Belongs to the plakin or cytolinker family. Many conflicts and frameshifts that might be strain-specific. Many conflicts and frameshifts that might be strain-specific. Many conflicts and frameshifts that might be strain-specific.