Major high molecular weight protein of desmosomes. Involved in the organization of the desmosomal cadherin-plakoglobin complexes into discrete plasma membrane domains and in the anchoring of intermediate filaments to the desmosomes. Homodimer. Interacts with COL17A1 (via cytoplasmic region). Associates (via C-terminal) with KRT5-KRT14 (via rod region), KRT8-KRT18 and VIM intermediate filaments. Interacts with DSC2. Interacts with PKP2. Interacts weakly with TMEM65 (By similarity). Innermost portion of the desmosomal plaque. Colocalizes with epidermal KRT5-KRT14 and simple KRT8-KRT18 keratins and VIM intermediate filaments network (PubMed:12802069). Localizes at the intercalated disk in cardiomyocytes (By similarity). Expressed in oral mucosa (at protein level) (PubMed:30479852). Expressed in arrector pili muscle (at protein level) (PubMed:29034528). Apparently an obligate constituent of all desmosomes. Resides predominantly in tissues and cells of stratified origin. 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 N-terminal region is required for localization to the desmosomal plaque and interacts with the N-terminal region of plakophilin 1. The three tandem plakin repeat regions in the C-terminus mediate binding to intermediate filaments. Ser-2849 is probably phosphorylated by a cAMP-dependent protein kinase. Phosphorylation on Ser-2849 probably affects its association with epidermal, simple cytokeratins and VIM intermediate filaments. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Minor isoform. Belongs to the plakin or cytolinker family. Desmoplakin entry