During cornification, a network of keratin intermediate filaments (KIF) and filaggrin (FLG) becomes crosslinked to the cornified envelope (CE). The FLG-KIF linkage occurs primarily through a specific lysine residue on the head domain of type II keratin chains, which can crosslink with several CE proteins including loricrin, SPRs, envoplakin and involucrin (Dale et al. 1978, Manabe et al. 1991, Mack et al. 1993, Steinert et al. 1995, Candi et al. 1998). This FLG-KIF crosslinking is believed to organise intermediate filaments into bundles, which stabilize the keratin network (Steinert et al. 1981, Candi et al. 2005) and facilitate the collapse and flattening of cells in the outermost stratum corneum to produce squames. Cell flattening can occur in the absence of FLG, but at the ultrastructural level loss-of-function mutations in FLG are associated with disorganized keratin filaments, impaired lamellar body loading and abnormal architecture of the lamellar bilayer (Gruber et al. 2011).