NTMT1 (N-terminal Xaa-Pro-Lys N-methyltransferase 1) is a distributive alpha-N-methyltransferase that catalyzes mono-, di-, or tri-methylation of the N-terminal alpha-amino group in proteins containing specific motifs such as [Ala/Gly/Ser]-Pro-Lys when the initiator methionine is cleaved 1. The enzyme operates through a random sequential Bi Bi kinetic mechanism and performs multiple methylations via a distributive mechanism 1. NTMT1 methylates critical cellular proteins including RCC1, SET, CENPA, and others, with particular importance for mitotic spindle organization and chromosome 9 through its action on RCC1 23. Disease relevance is significant, as NTMT1 is overexpressed in various cancers including gastrointestinal and colorectal cancers, where high expression correlates with poor prognosis 41. The enzyme's methylation activity can be detected in plasma cell-free DNA, making it a promising biomarker for colorectal cancer diagnosis with 91.2% sensitivity for CRC detection 5. Clinically, NTMT1 represents an attractive therapeutic target, with selective inhibitors and PROTAC degraders showing anti-proliferative effects in colorectal cancer cell lines and potential to induce immunogenic cell death responses 63.