A human α-N-acetylgalactosaminidase (NAGAL) polypeptide as set forth in SEQ ID NO: 1 or a functionally active variant thereof having at least 80% sequence identity to SEQ ID NO: 1 or a functionally active fragment thereof, modified such that: a first amino acid, corresponding to asparagine 213 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine; or a second amino acid, corresponding to cysteine 326 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine; or a first amino acid, corresponding to asparagine 213 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine, and a second amino acid, corresponding to cysteine 326 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine; and further comprising S to E substitution at an amino acid position corresponding to the position of amino acid 171 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, and A to L substitution at an amino acid position corresponding to the position of amino acid 174 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, whereby the modified human NAGAL polypeptide or functionally active variant or fragment thereof exhibits α-galactosidase activity. a first amino acid, corresponding to asparagine 213 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine; or a second amino acid, corresponding to cysteine 326 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine; or a first amino acid, corresponding to asparagine 213 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine, and a second amino acid, corresponding to cysteine 326 of human NAGAL polypeptide as set forth in SEQ ID NO: 1, is substituted with one, two or three amino acids each independently selected from the group consisting of alanine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine; and