Tmem106b-KO Mouse

TMEM106B, a lysosomal transmembrane protein, is crucial in regulating multiple aspects of lysosomal function [4]. It also plays a role in myelin lipid metabolism by interacting with galactosylceramidase [5]. Mutations in TMEM106B are risk factors for diverse neurodegenerative diseases [1].

Genetic variation in TMEM106B influences the risk and presentation of neurodegenerative diseases, especially frontotemporal dementia (FTD) caused by mutations in the progranulin gene (GRN) [6]. However, full deletion and partial reduction of TMEM106B in mouse and iPSC-derived human cell models of GRN deficiency did not reverse disease-associated phenotypes, suggesting that lowering TMEM106B levels may not be a viable therapeutic strategy for treating FTD-GRN [7].

In addition, TMEM106B has been found to form amyloid filaments in human brains in an age-dependent manner, which are present in various neurodegenerative diseases [3,6,8,9]. It can also serve as an alternative receptor for SARS-CoV-2 entry into angiotensin-converting enzyme 2 (ACE2)-negative cells [2].

In summary, TMEM106B is integral for lysosomal function and myelin lipid metabolism. Its role in neurodegenerative diseases, especially those related to GRN-associated FTD, has been studied using genetic models. The formation of amyloid filaments and its function as a viral entry receptor further highlight its significance in both neurological and infectious disease contexts.