[10] It is found in the membrane of a lysosome (transmembrane protein) and has its highest expression in the central nervous system, specifically within neurons and oligodendrocytes.

TMEM106B can form amyloid fibrils in a variety of neurodegenerative diseases and in neurologically healthy individuals, which have been structurally characterized by Cryo-EM.

[20] Typically, lysosomes are trafficked along a microtubule by a motor protein and it has been observed that TMEM106B may play an important role in this process.

[18] In knock-out studies of TMEM106B inappropriate clustering of lysosomes is observed at the nucleus, and it has been shown this phenotype can be rescued by re-introducing TMEM106B into the system.

When TMEM106B levels are increased a reduction in vATPase activity is observed and the lysosome is unable to maintain an acidic environment.

[23] A study performed in 515 FTLD-GRN with TDP-43 inclusion cases, including 89 individuals carrying pathogenic mutations in the granulin (GRN) gene, a known cause of familial FTLD-GRN identified a single nucleotide polymorphism (SNP), rs1990622, located 6.9 kilobases downstream of the TMEM106B gene (chromosome 7p21) as a genome-wide signal.

[23][26] Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes progressive loss of motor neurons that control movement.

TDP-43 aggregates and C9ORF72 mutations have been identified as important pathological and genetic markers, and therefore TMEM106B was investigated for its potential association to ALS.

Progranulin (PGRN) is a glycoprotein that has been identified as another important protein for lysosomal function in neurons and microglia, particularly during aging and neurodegenerative disease.

[31] Studies performed in vitro and in vivo, increasing and decreasing levels of TMEM106B, found that PGRN seems to be indirectly modulated by TMEM106B by impacting lysosomal functions.

Analysis of the HapMap database identified a nonsynonymous single-nucleotide polymorphism rs3173615 (p.T185S) in perfect linkage disequilibrium with rs1990622, that my represent the functional variant driving the association.

[33] vATPases are proton pumps found on cell membranes that are in charge of acidifying multiple organelles, including lysosomes.

It has been shown with increased level of TMEM106B there is excessive binding to MAP6 which impairs transport of the lysosome along the microtubule and leads to accumulation of swollen vacuoles in inappropriate places within the cell.