Tnfrsf1a, also known as the gene encoding the 55 kDa TNF receptor (formerly termed TNFR1), is a crucial part of the tumor necrosis factor (TNF) receptor superfamily. It plays a vital role in inflammation-related processes as it binds to TNF-α, a proinflammatory cytokine, and is involved in the regulation of the innate immune response [1]. Mutations in Tnfrsf1a can lead to TNF-receptor-associated periodic syndrome (TRAPS), an autoinflammatory disorder [1].

In the context of myocardial infarction, monocytes recruited to the brain after the event augment sleep. They generate TNF in the thalamic lateral posterior nucleus, which engages Tnfrsf1a-expressing glutamatergic neurons to increase slow wave sleep pressure. Disrupting sleep-related Tnfrsf1a signaling in this context increases cardiac sympathetic input and promotes monocyte influx, worsening cardiac function [2]. In multiple myeloma, overexpression of Tnfrsf1a confers carfilzomib resistance, possibly by dampening antitumor immunity through suppressing the expression of MHC genes and cell adhesion molecules [4]. In head-and-neck cancer patients, a specific polymorphism (−610 T > G, rs4149570) of Tnfrsf1a is related to the occurrence of malnutrition, with the TT genotype being an independent predictor of severe malnutrition and higher risk of critical weight loss [3].

In conclusion, Tnfrsf1a is essential in regulating inflammation and immune-related responses. Its role in diseases such as autoinflammatory syndromes, myocardial infarction, multiple myeloma, and head-and-neck cancer-related malnutrition has been revealed through various studies. Understanding Tnfrsf1a functions, especially through in-vivo models like those related to the above-mentioned disease conditions, can potentially provide new insights for disease treatment and management.