Tnfrsf11a, also known as receptor activator of nuclear factor kappa B (RANK), is a gene encoding a receptor that has a critical role in osteoclast function [3]. It is involved in the RANK signalling pathway, which provides insights into osteoclastogenesis, activation of bone resorption, and how hormonal signals impact bone structure and mass [1].

In asthma, Tnfrsf11a deficiency in Tnfrsf11a+/- mice remarkably attenuated the house dust mite (HDM)-induced signal transducer and activator of transcription 3 (STAT3) action and remodeling protein expression, suggesting its role in HDM-induced airway remodeling [2]. In sclerosing bone dysplasias, various Tnfrsf11a mutations have been associated with dysosteosclerosis (DOS) rather than osteopetrosis as previously hypothesized. Different mutations in Tnfrsf11a lead to the production of aberrant mutant RANK proteins, expanding the understanding of the genotype-phenotype relationship in these disorders [4,5,6,7].

In conclusion, Tnfrsf11a is essential for osteoclast function and is involved in pathways related to bone remodeling and airway remodeling in asthma. Gene-knockout or mutant mouse models have been crucial in revealing its role in these biological processes and associated diseases, helping to understand the molecular mechanisms underlying bone and airway-related disorders.