Tm4sf19, a member of the tetraspanin family, has diverse functions. It is involved in regulating lysosomal activity, cytoskeletal rearrangements, and cell adhesion. It impacts pathways related to inflammation, metabolism, and bone resorption, and is thus of biological importance in understanding obesity, osteoporosis, and related diseases. Genetic models, such as knockout mice, have been crucial in studying its functions [1,2].

In obesity, Tm4sf19 deletion in male mice fed a high-fat diet reduces lipid-associated macrophage (LAM) accumulation, increases restorative macrophages, and improves insulin sensitivity and energy expenditure by promoting adipocyte hyperplasia instead of hypertrophy [1]. In osteoporosis, Tm4sf19 deficiency in mice inhibits osteoclast multinucleation and prevents bone loss as it interacts with integrin αvβ3 through its large extracellular loop (LEL), regulating cytoskeletal rearrangements [2]. In collagen-induced arthritis, inhibition of Tm4sf19 by LEL-Fc reduces inflammation and bone destruction by suppressing TLR4-mediated inflammatory signaling and abnormal osteoclast activation [3].

In conclusion, Tm4sf19 plays essential roles in metabolic and skeletal-related diseases. Gene knockout models in mice have revealed its functions in obesity-induced inflammation, metabolic dysfunction, and bone-related pathologies, providing insights for potential therapeutic strategies targeting these disease areas.

References:

1. Choi, Cheoljun, Jeong, Yujin L, Park, Koung-Min, Kim, Jong Kyoung, Lee, Yun-Hee. 2024. TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction. In Nature communications, 15, 2779. doi:10.1038/s41467-024-47108-8. https://pubmed.ncbi.nlm.nih.gov/38555350/

2. Park, Sujin, Heo, Jin Sun, Mizuno, Seiya, Takahashi, Satoru, Kim, Seong-Jin. 2023. Tm4sf19 deficiency inhibits osteoclast multinucleation and prevents bone loss. In Metabolism: clinical and experimental, 151, 155746. doi:10.1016/j.metabol.2023.155746. https://pubmed.ncbi.nlm.nih.gov/38016540/

3. Park, Sujin, Yoon, Kwiyeom, Hong, Eunji, Kang, Dong-Woo, Kim, Seong-Jin. 2025. Tm4sf19 inhibition ameliorates inflammation and bone destruction in collagen-induced arthritis by suppressing TLR4-mediated inflammatory signaling and abnormal osteoclast activation. In Bone research, 13, 40. doi:10.1038/s41413-025-00419-y. https://pubmed.ncbi.nlm.nih.gov/40128226/