[12] The DSP gene is located on chromosome 6p24.3, containing 24 exons and spanning approximately 45 kDa of genomic DNA.

[15] A crystal structure of part of the plakin domain has been resolved,[16] while the entire plakin domain has been elucidated using small angle X-ray scattering which revealed a non-linear structure, an unexpected result considering spectrin repeats are observed in linear orientations.

[17] The C-terminal region of desmoplakin is composed of three plakin repeat domains, termed A, B and C, which are essential for coalignment and binding of intermediate filaments.

[14][18][19] Located at the most distal C-terminus of desmoplakin is a region rich in glycine–serine–arginine; it has been demonstrated that serine phosphorylation of this domain may modify desmoplakin-intermediate filament interactions.

In cardiomyocytes, desmoplakin forms desmosomal plaques with the intermediate filament desmin, whereas in endothelial cells cytokeratin type intermediate filaments are recruited, and vimentin in arachnoid and follicular dendritic cell types.

A case of compound heterozygosity for two DSP nonsense mutations resulting in lethal acantholytic epidermolysis bullosa has been reported.