The alternative protein translated from the TNFR1-d2 isoform carrying the p.(Thr79Met) pathogenic variant alters TNFR1 and TNFR1-d2 signalling pathways, and this gain of function could account for the pathophysiology of TRAPS in these patients and could represent a target for the development of new therapies for patients with inflammatory diseases. This evidence concerns the gene TNFRSF1A and TNF receptor 1-associated periodic fever syndrome.