Trypsin domain-containing protein 1 (TYSND1)

Trypsin domain-containing protein 1 (TYSND1) is a peroxisomal protease that specifically cleaves N-terminal (PTS2) and C-terminal (PTS1) peroxisomal targeting signals from precursor proteins, enabling their proper import and maturation within the peroxisome[1][2][6][8]. This processing is crucial for enzymes involved in the peroxisomal β-oxidation of very-long-chain fatty acids, plasmalogen synthesis, and phytanic acid metabolism[2][4][7]. The full-length protein undergoes autocleavage to generate smaller isoforms, a process that may regulate its activity[6]. TYSND1 deficiency impairs peroxisomal function, resulting in reduced fatty acid metabolism, abnormal lipid composition, male infertility in mouse models, and phenotypes overlapping with peroxisomal biogenesis disorders such as Zellweger syndrome and Rhizomelic chondrodysplasia punctata[1][4]. TYSND1 is classified as a trypsin-like cysteine endopeptidase and represents a noncanonical therapeutic target due to its central role in peroxisome biology, although no drugs currently target this protein directly[2][4][9].

Other names

TYSND1Trypsin like peroxisomal matrix peptidase 1Peroxisomal leader peptide-processing protease15 kDa form, 45 kDa form (related to molecular weight isoforms)NET41MGC34695Trypsin domain-containing protein 1Peroxisomal cysteine endopeptidasePeroxisomal matrix protein-processing protease

Not applicable (no approved drug mechanisms directly targeting TYSND1; experimental inhibition by N-ethylmaleimide, a cysteine protease inhibitor, abolishes TYSND1 activity)