Kazrin (KAZN) is an evolutionarily-conserved cytoplasmic and nuclear protein that was identified as a binding partner of periplakin (PPL), a component of epidermal desmosomes (DS) and the cornified envelope (CE) (Groot et al. 2004).
Kazrin has at least 5 different isoforms. Overexpression of the short isoform kazrinE stimulates the terminal differentiation of cultured human keratinocytes and is associated with a reduction in F-actin content, disruption of DS assembly, and changes in cell shape. Overexpression of activated RhoA rescues the effects on cell shape and adhesion. Conversely, knockdown of the longest isoform kazrinA impairs terminal differentiation, independently of RhoA activity (Sevilla et al. 2008a). KazrinE colocalizes with stabilized microtubules in differentiating keratinocytes (Nachat et al. 2009). All KAZN isoforms can form complexes with one another (Nachat et al. 2009), suggesting that like periplakin and envoplakin, it may form part of the cortical scaffold that integrates the actin cytoskeleton with DS (Ruhrberg et al. 1997, Kalinin et al. 2001, Groot et al. 2004). In Xenopus embryos, depletion of endogenous KAZN results in striking defects in axial elongation, muscle and notochord differentiation, and epidermal morphogenesis. These effects are believed to be due to disruption of cell-cell junctions (Sevilla et al. 2008b, Cho et al. 2010). However, mice with a knockout that removes exons 5-15 of KAZN had normal epidermal morphogenesis and homeostasis (Chhatriwala et al. 2012).