The cell uses the cytoskeleton in virtually every aspect of cell survival and function. One primary function of the cytoskeleton is to connect to and stabilize intercellular junctions. To accomplish this task, microtubules, actin filaments, and intermediate filaments utilize cytolinker proteins, which physically bind the cytoskeletal filament to the core proteins of the adhesion junction. The plakin family of linker proteins have been in the spotlight recently as critical components for embryo survival and, when mutated, the cause of diseases such as muscular dystrophy and cardiomyopathies. Here, we reveal the dynamics of a recently discovered plakin binding protein, kazrin (kaz), during early mouse development. Kaz was originally found in adult tissues, primarily epidermis, linking periplakin to the plasma membrane and colocalizing with desmoplakin in desmosomes. Using reverse transcriptase-polymerase chain reaction, Western blots, and confocal microscopy, we found kaz in unfertilized eggs associated with the spindle apparatus and cytoskeletal sheets. As quickly as 5 min after egg activation, kaz relocates to a diffuse peri-spindle position, followed 20–30 min later by clear localization to the presumptive cytokinetic ring. Before the blastocyst stage of development, kaz associates with the nuclear matrix in a cell cycle-dependent manner, and also associates with the cytoplasmic actin cytoskeleton. After blastocyst formation, kaz localization and potential function(s) become highly complex as it is found associating with cell–cell junctions, the cytoskeleton, and nucleus. Postimplantation stages of development reveal that kaz retains a multifunctional, tissue-specific role as it is detected at diverse locations in various embryonic tissue types. Developmental Dynamics 234:201–214, 2005. © 2005 Wiley-Liss, Inc.