This family includes Transmembrane protein 106A/B/C, type II transmembrane proteins which have homology to the late embryogenesis abundant-2 (LEA-2) domain []. TMEM106A has been identified as a key factor to regulate macrophage activation and a tumor suppressor in gastric, renal cancer and nonsmall-cell lung carcinoma (NSCLC), being an interesting therapeutic target for the management of NSCLC [, ]. TMEM106B localises to late endosomes and lysosomes, and it is involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with MAP6 []. Its overexpression is associated with familial frontotemporal lobar degeneration []. It has also been identified as a protein required for productive SARS-CoV-2 infection []. Structural analysis of LEA-2 domains revealed that they have a long, conserved lipid-binding groove, implying that TMEM106B and its homologues, Vac7 and Tag1 from yeast, may all be lipid transfer proteins in the lumen of late endocytic organelles.
