Filaggrin (FLG)

^[1]^[2]^[3]

Function

promotes production of natural moisturizing factors & the lipid matrix, which acts like mortar, keeping keratinocytes in the horny layer together^[3]
aggregates keratin intermediate filaments & promotes disulfide-bond formation among the intermediate filaments during terminal differentiation of mammalian epidermis
filaggrin is initially synthesized as a large, insoluble, highly phosphorylated precursor containing many tandem copies of 324 AA, which are not separated by large linker sequences
during terminal differentiation it is dephosphorylated & proteolytically cleaved
the N-terminal of the mature protein is heterogeneous, & is blocked by the formation of pyroglutamate
undergoes deimination of some Arg (citrullination)

defects in FLG are the cause of ichthyosis vulgaris
defects in FLG may be the cause of susceptibility to atopic dermatitis type 2
loss-of-function mutation in FLG perturbs the skin barrier
- increasing transepidermal water loss, resulting in xerosis
- the lack of epidermal lipids also reduces production of antimicrobial peptides & facilitates allergen penetration of the skin inducing allergic sensitization