Tnfsf14, also known as LIGHT (Lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells), is a member of the tumor necrosis factor superfamily. It is involved in multiple biological processes and signaling pathways. LIGHT can interact with several receptors, such as Herpes virus entry mediator and Lymphotoxin β receptor, and is crucial in immunological regulation, fibrosis, and energy metabolism-related processes [1-10].

In mouse models, Tnfsf14-/-mice show protection from ovariectomy-dependent bone loss, indicating that LIGHT mediates such bone loss, suggesting potential benefits of LIGHT antagonism for postmenopausal osteoporosis patients [4]. Tnfsf14-/-and Rag-/ Tnfsf14-(DKO) mice have lower visceral White Adipose Tissue (vWAT) weight when fed a normal diet, and DKO mice show potential browning effect in inguinal WAT (iWAT), highlighting the impact of Tnfsf14 on adipose tissue phenotype [1]. Also, LIGHT deficiency in mice accelerates browning in subcutaneous white adipose tissue during acute cold stress, and Tnfsf14-derived peptides can reduce high-fat diet-induced glucose intolerance, insulin resistance, and liver steatosis in a mouse model of obesity [2,3].

In conclusion, Tnfsf14 is a key regulator in various biological functions, especially in bone metabolism, adipose tissue regulation, and glucose homeostasis. The use of Tnfsf14 KO and related mouse models has provided valuable insights into its role in postmenopausal osteoporosis, obesity, and related metabolic diseases, offering potential therapeutic directions for these conditions.