Stratum granulosum

Epidermis · Layer 3 Filaggrin Barrier is made here

Three to five cell layers in which the keratinocyte dismantles itself: nucleus and organelles are lost, keratohyalin granules release filaggrin to aggregate keratin, and lamellar bodies discharge the intercellular lipid that becomes the permeability barrier.

Detail

Keratohyalin granules
Contain profilaggrin, cleaved to filaggrin, which bundles keratin filaments into the dense corneocyte core; its breakdown products form natural moisturising factor
Lipid discharge
Lamellar bodies empty ceramides, cholesterol and free fatty acids into the intercellular space at the granular-corneal interface, sealing the barrier
Cornified envelope
Involucrin and loricrin are cross-linked by transglutaminase 1 beneath the plasma membrane
Adhesion
Desmoglein 1 predominates from here upwards, so this is the level at which anti-Dsg1 antibodies and staphylococcal toxin cause splitting

When it goes wrong

Filaggrin (FLG) loss-of-function mutation

Ichthyosis vulgaris and the strongest known genetic risk factor for atopic dermatitis: a leaky barrier admits allergens and drives the atopic march to asthma and rhinitis

Staphylococcus aureus exfoliative toxin A or B cleaving desmoglein 1 (staphylococcal scalded skin syndrome, bullous impetigo)

Split at the granular layer, positive Nikolsky sign, mucous membranes spared because Dsg3 compensates there; blister fluid is sterile in scalded skin syndrome because the toxin is blood-borne

Transglutaminase 1 (TGM1) mutation

Lamellar ichthyosis, with a collodion membrane at birth and lifelong scaling from a defective cornified envelope

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