While deletion of HOIP and HOIL-1 in KCs results in massive skin inflammation and early postnatal lethality, which is delayed upon compound removal of TNF or TNFR1 [79], the phenotypes of mice lacking functional SHARPIN or keratinocyte-selective OTULIN are respectively milder or fully rescued upon removal of TNFR1 [78, 84, 87, 88], indicating that different molecular mechanisms regulate KC lethality in these distinct genetic contexts. The gene discussed is TNFRSF1A; the disease is keratoconus.