Clinical perspectiveTargeting of TNFRSF and TNFSF is a common therapeutic strategyThere are possible advantages of using PGRN or Atsttrin instead of conventional TNF blockers due to additional inhibition of DR‐3 and activation of TNFRIIAutoantibodies to PGRN regularly target the binding region within the N‐terminal 112 amino acids and not the parts of PGRN that are constitutive of Atsttrin; however, their affinity for Atsttrin has not been excludedRisk of side effects concerning susceptibility to infectious diseases, emergence of new autoimmune phenomena, or cancer remains unclear. This evidence concerns the gene TNFRSF25 and cancer.