To address whether SHARPIN truly acts as an integrin inhibitor in vivo, we made use of the Tnfr1-/-Sharpincpdm/cpdm double knockout mice, in which the skin thickening (Fig 1A), chronic inflammation and dermatitis, typical to Sharpincpdm/cpdm mice, are absent [16,17]. The gene discussed is TNFRSF1A; the disease is skin disorder.