TMEM106B, a lysosomal transmembrane protein, is involved in regulating lysosomal function and myelin lipid metabolism [3,4]. It may also play a role in ACE2-independent SARS-CoV-2 cell entry [2]. Mutations in TMEM106B are risk factors for diverse neurodegenerative diseases [1].

In mouse models, TMEM106B deficiency significantly decreases levels of myelin lipids, galactosylceramide and sulfatide, and increases galactosylceramidase activity, suggesting its role in regulating myelin lipid metabolism [4]. However, full deletion or partial reduction of TMEM106B in mouse and iPSC-derived human cell models of GRN deficiency did not reverse disease-associated phenotypes, indicating that lowering TMEM106B levels may not be a viable therapeutic strategy for treating FTD-GRN [5].

In conclusion, TMEM106B is crucial for lysosomal function and myelin lipid metabolism. Mouse models have provided insights into its functions and potential implications in neurodegenerative diseases, such as frontotemporal dementia. Although reducing TMEM106B levels may not be a therapeutic solution for FTD-GRN, understanding its role can still contribute to the understanding of neurodegenerative disease mechanisms [1,3,4,5].