In humans, the Hex-mediated GnT-I-dependent truncation pathway is known to facilitate, at least in some tissues including neutrophils, the production of paucimannosidic proteins. Human Hex isoenzymes are assembled with alpha and beta subunits encoded by the HEXA and HEXB genes, respectively. From these two subunits, isoenzymes such as Hex A (one alpha and one beta subunit), Hex B (two beta subunits) and Hex S (two alpha subunits) are generated. Both Hex A and Hex B are reported to play important functional roles in human, particularly in the lysosomal degradation of gangliosides. Recently, both HEXA and HEXB were documented to mediate protein paucimannosylation in human neutrophils and may therefore also be the main driver for the elevated production of paucimannosidic proteins during cancer development. Recent in vitro observations have suggested other noncanonical truncation pathways with direct core fucosylation of paucimannosidic proteins in vertebrates, but this remains to be validated Hex A and Hex B isoenzymes are mainly present in the azurophilic granules of human neutrophils as a result of a proposed targeting-by-timing mechanism that supposedly directs these enzymes to this compartment during neutrophil development. Recently, granule-specific glycosylation was shown in neutrophils featuring prominent paucimannosylation in the azurophilic granules an observation that was suggested to arise from a "glycosylation-by-timing" mechanism yet to be documented. More widely across vertebrate species, the biosynthesis of paucimannosidic proteins remains largely unstudied.