Endoplasmic reticulum-associated degradation of misfolded glycoproteins ensures only functional, correctly folded proteins exit from the endoplasmic reticulum and that misfolded ones are targeted for lysosomal degradation. Once located to the lysosome, epididymis-specific alpha-mannosidase (MAN2B2) can hydrolyse nondegraded oligosaccharides such as GlcNAc (Man)3 to GlcNAc (Man)2 quickly and GlcNAc (Man)2 to GlcNAc:Man slowly (Park et al. 2005, Venkatesan et al. 2009). MAN2B2 is ubiquitously expressed and 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.