Prolyl endopeptidase-like (PREPL)

Prolyl endopeptidase-like (PREPL) is a protein encoded by the PREPL gene and belongs to the prolyl oligopeptidase family of serine peptidases[3][1][2]. Structurally, PREPL shares significant homology with prolyl endopeptidase (PREP), featuring a β-propeller and a catalytic α/β-hydrolase domain[1][2][3]. However, unlike active family members, PREPL is thought to be catalytically inactive toward classic peptide or protein substrates, with only trace hydrolytic activity observed in experimental settings[3]. The prevailing hypothesis is that PREPL mediates cellular functions primarily through protein-protein interactions rather than direct substrate cleavage, possibly playing a regulatory role in protein complexes linked to growth and neuromuscular development[1][2][3]. Deletions or mutations in PREPL can cause congenital syndromes characterized by severe growth impairment and neuromuscular symptoms, including congenital myasthenic syndrome type 22[3]. There are currently no known approved drugs or small molecules targeting PREPL, and its value as a direct therapeutic target remains speculative.

Other names

Prolyl endopeptidase-likePREPLKIAA0436CMS22prolylendopeptidase-likeputative prolyl oligopeptidase

No confirmed mechanism as a drug target; biological role is likely via PPI rather than classic enzymatic activity