Lysosomal alpha-mannosidase (MAN2B1) belongs to a broad alpha-mannosidase family called class 2 alpha-mannosidases (CAZy glycosylhydrolase family 38, GH38). GH38 members are found in the Golgi complex, lysosomes, and cytosol where they are involved in either glycoprotein biosynthesis or catabolism. MAN2B1 (Liao et al. 1996, Berg et al. 1999) is involved in the sequential hydrolysis of mannose oligosaccharides sent to lysosomes for degradation. From the non-reducing end, MAN2B1 catalyses the hydrolysis of alpha(1,2), alpha(1,3) and alpha(1,6) mannosidic linkages (Beccari et al. 1999). Defects in the MAN2B1 gene cause alpha-mannosidosis (MIM:248500), a rare lysosomal storage disease. The disorder is characterised by a range of clinical phenotypes, the major manifestations being mental impairment, hearing impairment, skeletal changes, and immunodeficiency (Borgwardt et al. 2014, Riise Stensland et al. 2015).