Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides. The isozyme S is as active as the isozyme A on the anionic bis-sulfated glycans, the chondroitin-6-sulfate trisaccharide (C6S-3), and the dermatan sulfate pentasaccharide, and the sulfated glycosphingolipid SM2. The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide. Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A. Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. H2O + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-3-sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide = a beta-D-3-sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + N-acetyl-beta-D-galactosamine ganglioside GM2 (d18:1(4E)) + H2O = ganglioside GM3 (d18:1(4E)) + N-acetyl-beta-D-galactosamine ganglioside GM2 + H2O = ganglioside GM3 + N-acetyl-beta-D-galactosamine beta-D-GalNAc-(1->4)-alpha-L-IdoA-(1->3)-beta-D-GalNAc-4-sulfate-(1->4)-alpha-L-IdoA-(1->3)-D-GalNAc-4-sulfate + H2O = alpha-L-IdoA-(1->3)-beta-D-GalNAc-4-sulfate-(1->4)-alpha-L-IdoA-(1->3)-D-GalNAc-4-sulfate + N-acetyl-D-galactosamine H2O + N-acetyl-beta-D-6-sulfogalactosaminyl-(1->4)-alpha-L-iduronyl-(1->3)-N-acetyl-D-6-sulfogalactosamine = alpha-L-iduronyl-(1->3)-N-acetyl-D-6-sulfogalactosamine + N-acetyl-D-6-sulfogalactosamine Addition of GM2A stimulates the hydrolysis of sulfated glycosphingolipid SM2 and the ganglioside GM2. There are 3 beta-hexosaminidase isozymes: isozyme A (hexosaminidase A) is an heterodimer composed of one subunit alpha and one subunit beta (chain A and B); isozyme B (hexosaminidase B) is an homodimer of two beta subunits (two chains A and B); isozyme S (hexosaminidase S) is a homodimer of two alpha subunits. The composition of the dimer (isozyme A versus isozyme S) has a significant effect on the substrate specificity of the alpha subunit active site. Belongs to the glycosyl hydrolase 20 family.