PCMT1 encodes protein-L-isoaspartate (D-aspartate) O-methyltransferase, a highly conserved enzyme that repairs damaged proteins by catalyzing methyl esterification of abnormal L-isoaspartyl and D-aspartyl residues that form spontaneously in aging proteins 1. The enzyme functions both intracellularly and extracellularly, with unconventional secretion allowing repair of extracellular matrix proteins 1. PCMT1's repair activity requires S-adenosylmethionine as a methyl donor and is crucial for maintaining protein homeostasis 2. In disease contexts, PCMT1 exhibits complex roles across cancers. It promotes metastasis in ovarian and breast cancers by enhancing cell migration, adhesion, and invasion through interactions with extracellular matrix proteins like LAMB3 and activation of integrin-FAK-Src signaling 34. High PCMT1 expression correlates with poor prognosis and increased tumor progression in multiple cancer types 56. However, PCMT1 also demonstrates protective functions, particularly in kidney fibrosis where it prevents TGF-β receptor 2 deamidation and subsequent fibrotic signaling 1. Additionally, PCMT1 genetic variants influence neural tube defect risk, with Val120Val genotype conferring protection against spina bifida 7. The enzyme's dual roles highlight its importance in both protein repair and disease pathogenesis.